Analysis Tools|
Allele Symbol Allele Name Allele ID |
Gt(ROSA)26Sor+ wild type MGI:2176739 |
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| Summary |
1089 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit reduced survival ratio (<90%) at 25 weeks with dox treatment
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• mice treated with higher doses of doxycycline (dox) exhibit mortality as early as 2 weeks and 100% mortality rate by 5-6 weeks
• mice treated with a lower dox regiment show 90% mortality rate by 25 weeks after dox treatment initiation
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• mice treated with a combination of 2 mg/ml of doxycycline (dox) in drinking water coupled with 5 of 10 mg/kg intraperitoneal injection beginning at 3 months of age for 20 weeks develop disease phenotypes paralleling those of Friedreich's ataxia; this dox regiment was used for analysis
• mice exhibit reduced hind and front limb stride length at 12 and 24 weeks with dox treatment, indicating ataxic gait
• removal of dox results in rapid improvement in gait ataxia
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• dox treated mice fall faster off the rotarod than controls from 12 weeks onward with dox treatment
• removal of dox results in improvement on the rotarod
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• mice exhibit defects in forelimb muscular strength at 12 and 24 weeks with dox treatment
• removal of dox results in rapid improvement of muscle strength
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• mice exhibit reduced hind and front limb stride length at 12 and 24 weeks with dox treatment
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• dox treated mice exhibit decreased locomotor activity, showing a shorter distance traveled at 12 and 24 weeks with dox treatment
• removal of dox results in improvement in locomotor activity
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• cardiomyocytes show severe disorganization, with disorganized and irregular sarcomeres and enlarged mitochondria at 20 weeks of dox treatment
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• mice exhibit increased myocardial iron at 20 weeks of dox treatment, showing increased ferric iron staining and increased expression of iron metabolic proteins, ferritin and ferroportin
• removal of dox results in reduced iron and ferritin accumulation
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• mice exhibit excessive collagen deposition in hearts at 20 weeks of dox treatment, indicating cardiac fibrosis
• removal of dox results in reduced myocardial fibrosis
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• mice exhibit absence of P-waves at week 24 of dox treatment, suggesting an atrial conduction abnormality
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• mice exhibit an increase in QT interval duration at 12 and 24 weeks post dox treatment
• however, mice exhibit a normal ECG 12 weeks after dox removal
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• mice exhibit ventricular and posterior wall thickening by 24 weeks of dox treatment, indicating hypertrophic cardiomyopathy
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• in a minority of mice, cardiomyocytes show mitochondria with disorganized cristae and vacuoles at 20 weeks of dox treatment, suggesting mitochondrial degeneration
• removal of dox results in reduced mitochondrial abnormalities
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• cardiomyocytes have enlarged mitochondria at 20 weeks of dox treatment
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• mice exhibit weight loss at 25 weeks with dox treatment
• removal of dox results in rapid improvement in body weight
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• mice exhibit increased myocardial iron at 20 weeks of dox treatment, showing increased ferric iron staining and increased expression of iron metabolic proteins, ferritin and ferroportin
• removal of dox results in reduced iron and ferritin accumulation
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• heart shows reduced aconitase, an Fe-S containing enzyme, activity at 20 weeks of dox treatment
• removal of dox results in normal aconitase activity
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• cardiomyocytes show severe disorganization, with disorganized and irregular sarcomeres and enlarged mitochondria at 20 weeks of dox treatment
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• mice exhibit ventricular and posterior wall thickening by 24 weeks of dox treatment, indicating hypertrophic cardiomyopathy
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• cardiomyocytes have disorganized and irregular sarcomeres at 20 weeks of dox treatment
• removal of dox results in improved sarcomere organization
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• mice exhibit a decrease in axonal size in the spinal cord at 20 weeks of dox treatment
• however, the number of Purkinje cells and the cerebellar granular and molecular layers are not altered at 20 weeks of dox treatment
• removal of dox results in mild improvement in axonal size in the spinal cord
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• mice exhibit a decrease in myelin sheath thickness in the spinal cord at 20 weeks of dox treatment
• removal of dox results in mild improvement in myelin sheath thickness
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• photoreceptors are disrupted at 20 weeks of dox treatment
• removal of dox results in a reduction of disrupted photoreceptors
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• dorsal root ganglia neurons show an increase in condensed mitochondria at 20 weeks of dox treatment, with most cases showing empty vesicles associated with the condensed mitochondria, suggesting neuronal degeneration
• removal of dox results in fewer condensed, degenerating mitochondria in dorsal root ganglion neurons
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• mice exhibit an increase in degenerating retinal pigment epithelium cells with vacuoles at 20 weeks of dox treatment
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• photoreceptors are disrupted at 20 weeks of dox treatment
• removal of dox results in a reduction of disrupted photoreceptors
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• mice exhibit an increase in degenerating retinal pigment epithelium cells with vacuoles at 20 weeks of dox treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Friedreich ataxia | DOID:12705 | J:254962 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adult size is slightly reduced
• male mice are 14% smaller than controls by 20 weeks of age
• female mice are 11% smaller than controls by 20 weeks of age
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• males exhibit slower growth after 8 weeks of age
• females exhibit slower growth after 12 weeks of age
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• swollen subiliac lymph nodes
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| N |
• mice exhibit no overt myopathy
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice do not exhibit any evidence of active necrosis or regeneration
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• in some doxycycline-treated mice prior to CTX injection
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• increased collagen fibrils in the endomysial space in doxycycline-treated mice injected with CTX
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• in doxycycline-treated mice injected with CTX
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• aggressive in doxycycline-treated mice injected with CTX
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• increased skeletal muscle regeneration in doxycycline-treated mice injected with CTX
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• fragmented and irregular, consistent with impaired maturation at the ultrastructural level, in doxycycline-treated mice injected with CTX without an increase in acetylcholine receptor aggregations number and size compared with control mice
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• doxycycline-treated mice injected with CTX exhibit thickened muscle basement membrane, increased collagen fibrils in the endomysial space and aggressive muscular dystrophy compared with control mice
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• in doxycycline-treated mice injected with CTX compared with control mice
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• thickened muscle basement membrane in doxycycline-treated mice injected with CTX compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P5, but no at 3M
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• in female, but not male, mice
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• however, trabecular bone thickness is normal
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• in female, but not male, mice
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• in female, but not male, mice
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• at P5, but no at 3M
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• at P5, but no at 3M
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in mice fed standard chow
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• in mice fed a high-fat diet
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• in mice fed a high-fat diet
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• in mice fed a high-fat diet
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| N |
• mice fed a high-fat diet exhibit wild-type glucose tolerance, insulin sensitivity, and lipid homeostasis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are fertile and did not show any overt phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are fertile and did not show any overt phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are fertile and did not show any overt phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no mice are recovered at birth when exposed to doxycycline throughout pregnancy
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• of terminal end bud in mice treated with doxycycline from birth
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• at 4 and 6 weeks, mice treated with doxycycline from birth exhibit delayed mammary gland outgrowth compared with wild-type mice
• at 4 weeks, mice treated with doxycycline from birth exhibit distal ends without terminal end bud appearance unlike in wild-type mice
• however, outgrowth at 9 weeks and mammary epithelium architecture are normal
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• mice treated with doxycycline from birth exhibit reduced ductal elongation compared with wild-type mice
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• in mice treated with doxycycline from birth
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• in mice treated with doxycycline from birth
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• of terminal end bud in mice treated with doxycycline from birth
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• of terminal end bud in mice treated with doxycycline from birth
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• at 4 and 6 weeks, mice treated with doxycycline from birth exhibit delayed mammary gland outgrowth compared with wild-type mice
• at 4 weeks, mice treated with doxycycline from birth exhibit distal ends without terminal end bud appearance unlike in wild-type mice
• however, outgrowth at 9 weeks and mammary epithelium architecture are normal
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• mice treated with doxycycline from birth exhibit reduced ductal elongation compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no mice are recovered at birth when exposed to doxycycline throughout pregnancy
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• of terminal end bud in mice treated with doxycycline from birth
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• at 4 and 6 weeks, mice treated with doxycycline from birth exhibit delayed mammary gland outgrowth compared with wild-type mice
• at 4 weeks, mice treated with doxycycline from birth exhibit distal ends without terminal end bud appearance unlike in wild-type mice
• however, outgrowth at 9 weeks and mammary epithelium architecture are normal
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• mice treated with doxycycline from birth exhibit reduced ductal elongation compared with wild-type mice
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• in mice treated with doxycycline from birth
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• in mice treated with doxycycline from birth
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• of terminal end bud in mice treated with doxycycline from birth
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• of terminal end bud in mice treated with doxycycline from birth
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• at 4 and 6 weeks, mice treated with doxycycline from birth exhibit delayed mammary gland outgrowth compared with wild-type mice
• at 4 weeks, mice treated with doxycycline from birth exhibit distal ends without terminal end bud appearance unlike in wild-type mice
• however, outgrowth at 9 weeks and mammary epithelium architecture are normal
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• mice treated with doxycycline from birth exhibit defective lobuloalveolar differentiation during mid- and late pregnancy that persists in parturition compared with wild-type mice
• however, alveolar lumina are filled with milk
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• mice treated with doxycycline from birth exhibit reduced ductal elongation compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• formation arrested at the level of the forelimbs when foster mothers treated with doxycycline
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• tail outgrowth fails or is abnormal when foster mothers treated with doxycycline
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• complete lethality around E10 when foster mothers treated with doxycycline
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• posterior development arrested early when foster mothers treated with doxycycline
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• excessive neural tissue at the caudal end of the embry when foster mothers are treated with doxycycline
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• absence of notochord caudal to mid brain at E9.5 when foster mothers treated with doxycycline
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• few irregularly shaped somites when foster mothers treated with doxycycline
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• absence of allantois derivatives when foster mothers treated with doxycycline
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• excessive neural tissue at the caudal end of the embry when foster mothers are treated with doxycycline
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• complete lethality around E10 when foster mothers treated with doxycycline throughout development
• early lethality avoided if doxycycline induction delayed until E9.5
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• mesoderm development arrested by E12.5 when doxycycline treatment of foster mothers delayed until E9.5
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• posterior development arrested early when foster mothers treated with doxycycline throughout development
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• excessive neural tissue at the caudal end of the embry when foster mothers are treated with doxycycline throughout development
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• absence of notochord caudal to mid brain at E9.5 when foster mothers treated with doxycycline throughout development
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• notochord development arrested at the mid tail level by E12.5 when doxycycline treatment of foster mothers begins ast E9.5
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• few irregularly shaped somites when foster mothers treated with doxycycline throughout development
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• absence of allantois derivatives when foster mothers treated with doxycycline throughout development
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• excessive neural tissue at the caudal end of the embry when foster mothers are treated with doxycycline throughout development
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 12 weeks in doxycycline-treated mice
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• in doxycycline-treated mice
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• contracted kidneys with tubular atrophy, scarring, cyst formation and focal tubular regeneration in dead doxycycline-treated mice
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• in dead doxycycline-treated mice
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• from 4 weeks on in doxycycline-treated mice
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• fused from 4 weeks on in doxycycline-treated mice
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• doxycycline-treated mice exhibit progressive glomerular lesions and irregularities that progress to focal sclerosis unlike in control mice
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• focal sclerosis in doxycycline-treated mice that is elevated with time
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• focal tubular regeneration in dead doxycycline-treated mice
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• in dead doxycycline-treated mice
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• in doxycycline-treated mice
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• in dead doxycycline-treated mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| focal segmental glomerulosclerosis | DOID:1312 |
OMIM:PS603278 |
J:197989 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• normal at birth
• 100% dead by day 300
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• greatly reduced red blood cell number
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• massively increased number of reticulocytes in the circulation
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• splenomegaly
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• disrupted follicle structure
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• dyspnea, difficulty breathing
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• angiodysplasia-like lesions in the ileum and colon
• hemorrhage of capillaries and thin walled vascular channels
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• no pulmonary artery hypertrophy
• dilated preacinar pulmonary arteries
• disorganized adventitia
• thin tunica media
• reduced wall thickness
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• regions of both intestinal and pulmonary arteries lack smooth muscle
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• massive intestinal hemorrhage, mostly in the cecum or at the ileocecal junction
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• splenomegaly
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| N |
• bone marrow morphology is normal
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| N |
• blood clotting function is normal
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• massive intestinal hemorrhage, mostly in the cecum or at the ileocecal junction
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• large solitary polyps develop in the small and large intestine
• some with irregular tubular cysts and distorted glands
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• regions of both intestinal and pulmonary arteries lack smooth muscle
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• splenomegaly
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• disrupted follicle structure
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in cultured neural crest cells treated with tamoxifen
• however, removal of tamoxifen restores normal proliferation and differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• show a reduced body weight at 4 weeks after birth compared with those of wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit reduced ear melanization compared with wild-type mice
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• mice exhibit light hair color compared with wild-type mice
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• mice exhibit reduced ear melanization compared with wild-type mice
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• mice exhibit reduced ear melanization compared with wild-type mice
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• mice exhibit reduced ear melanization compared with wild-type mice
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• mice exhibit light hair color compared with wild-type mice
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• mice exhibit reduced ear melanization compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• whether treated with doxycycline or not, mice are viable
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• small increase in bone formation in the calvaria
• however, bone mineral density is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile; no detailed analysis available
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile with no gross behavioral or visible abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mouse embryonic fibroblasts exposed to TAT-cre exhibit cell death unlike cells not exposed to TAT-cre
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• C7 transformation to T1 in all mice with ectopic ribs on C7
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• C1 to C2 in 2 of 7 mice
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• posterior transformation of the axis as in null mice
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• T1 to T2 in 5 of 7 mice
• T13 to L1 in all mice
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• C7 to T1 in all mice with ectopic ribs on C7
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• L6 to S1 in all mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P20, optic nerves exhibit disordered lamination in the direct circumference compared to in wild-type mice
• however, lamination in the periphery is normal
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• at P180
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• with rossette formation
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• in 80% of mice
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• at P180 near the optic nerve in 60% of mice
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• at P180, electroretinogram waveforms and parameters are different than in wild-type mice
• at P180, the ratio between the amplitudes of oscillatory potentials and b-waves is higher than in wild-type mice
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• at P30 and P180, photopic b-wave and photopic 30 Hz flicker amplitudes are smaller than in wild-type mice
• at P180, scotopic and photopic oscillatory potential amplitudes are smaller than in wild-type mice
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• at P180, scotopic a-wave and b-wave amplitudes are smaller than in wild-type mice
• at P180, scotopic and photopic oscillatory potential amplitudes are smaller than in wild-type mice
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• in the eye at P180
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• with rossette formation
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• at P20, optic nerves exhibit disordered lamination in the direct circumference compared to in wild-type mice
• however, lamination in the periphery is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile; no further phenotypic analyses are available
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are healthy with normal function of the respiratory chain
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• detected in females by 5 weeks of age
• females are about 11% heavier than control littermates at 20 weeks of age
• males are about 7% heavier than control littermates at 20 weeks of age
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• increased weight gain on a high fat diet compared to diet matched controls
• increase in fat mass on a high fat diet is more pronounced in females
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• increase in food intake on both standard and high fat diets
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• increase in fat mass in both males and females
• increase is less than in homozygous mice
• increase in fat mass on a high fat diet is more pronounced in females
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• increase in epigonadal and abdominal white adipose tissues
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• increased weight gain on a high fat diet compared to diet matched controls
• increase in fat mass on a high fat diet is more pronounced in females
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• in females at 20 weeks of age
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• in females at 20 weeks of age
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• in females at 20 weeks of age
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• in females at 20 weeks of age
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• in males at 20 weeks of age when corrected for fat mass
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• in females on a high fat diet and in males on a standard diet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile as heterozygotes or homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile with no reported gross physical or behavioral abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile with no reported gross physical or behavioral abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile with no reported gross physical or behavioral abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fusion gene is expressed ubiquitously; with tissue hypoxia, luciferase expression is enhanced in those tissues
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased survival compared to wild-type controls carrying either Tg(MMTV-cre)1Mam or Tg(MMTV-cre)4Mam
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• some mice develop blood vessel lesions
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• crypt-derived organoids rapidly form clonogenic spheroids in vitro when treated with doxycycline, in which self-renewal capacity correlates with expression of the inserted sequence
• doxycycline-induced spheroid cultures deprived of doxycycline and treated with R-Spondin retain the ability to form major lineages of untransformed intestinal epithelium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile and displayed no gross abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 5-fold increased in aberrant elongating spermatid heads
• spermatids exhibit an increase in di-methylation of histone H3 Lys4 compared with control cells
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• reduced XY synapsis in spermatocytes
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• at 4 and 19 weeks
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|
|
• at 4 and 19 weeks
|
|
• to a greater degree when heterozygotes are mated
|
|
• at 4 weeks but not 19 weeks
|
|
|
• 5-fold increased in aberrant elongating spermatid heads
• spermatids exhibit an increase in di-methylation of histone H3 Lys4 compared with control cells
|
|
• reduced XY synapsis in spermatocytes
|
|
|
• spermatocytes exhibit persistent double-strand DNA breaks in meiotic prophase unlike in control cells
|
|
|
• spermatocytes exhibit persistent double-strand DNA breaks in meiotic prophase unlike in control cells
|
|
|
• at 4 and 19 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal body weight
|
| N |
• doxycycline-treated mice exhibit normal glucose homeostasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal body weight
|
| N |
• doxycycline-treated mice exhibit normal glucose homeostasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal energy homeostasis
|
|
• in fasting doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
| N |
• doxycycline-treated mice exhibit normal body weight
|
| N |
• pancreatic beta-cell morphology is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice spend more time in an averse lit compartment than wild-type mice
|
|
• compared to wild-type mice following 10 minute restraint stress
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Defects of cardiac mitochondria and mitochondrion-associated membranes in Gt(ROSA)26Sortm37(H1/tetO-RNAi:Tafazzin)Arte/Gt(ROSA)26Sor+ mice
|
• after 8 months, cardiac muscles from doxycycline-treated mice exhibit abnormal mitochondria compared with wild-type mice
• after 8 months, cardiac ventricles from doxycycline-treated mice exhibit poorly arrayed sarcomeres compared to in wild-type mice
|
|
• at 8 months, doxycycline-treated mice exhibit increased left ventricular diameter and volume both at end diastole and end systole and reduced diastolic thickness of left ventricular posterior wall and interventricular septum compared with wild-type mice
• at 8 months, doxycycline-treated mice exhibit a reduction of left ventricular mass (LV wall volume) compared with wild-type mice
|
|
• at 8 months in a doxycycline-treated mice
|
|
• at 8 months, doxycycline-treated mice exhibit reduced fractional shortening and ejection fraction compared with wild-type mice
|
|
• doxycycline-treated mice exhibit an increase in mitochondria in the heart and muscles compared to in wild-type mice
|
|
• doxycycline-treated mice exhibit an increase in mitochondria in the heart and muscles compared to in wild-type mice
|
|
• in doxycycline-treated mice after 8 months
|
|
• after 8 months, cardiac muscles from doxycycline-treated mice exhibit abnormal mitochondria compared with wild-type mice
• after 8 months, cardiac ventricles from doxycycline-treated mice exhibit poorly arrayed sarcomeres compared to in wild-type mice
|
|
• at 8 months, doxycycline-treated mice exhibit reduced fractional shortening and ejection fraction compared with wild-type mice
|
|
• after 8 months, cardiac ventricles from doxycycline-treated mice exhibit poorly arrayed sarcomeres compared to in wild-type mice
|
|
• at 2 months, skeletal muscles from doxycycline-treated mice exhibit increased number of mitochondria with various inner membrane abnormalities compared to in wild-type mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Barth syndrome | DOID:0050476 |
OMIM:302060 |
J:167527 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile; used for cre reporter expression analysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile; used for cre reporter expression analysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile; used for cre reporter expression analysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile; used for cre reporter expression analysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile; used for cre reporter expression analysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have a strong reduction in body weight compared to littermate controls
|
|
• mice are obtained at half (12.5%) of the expected (25%) frequency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice heterozygous for this targeted reporter gene are viable, fertile and exhibit no gross physical or behavioral abnormalities
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and fertile with no overt abnormalities
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Granulocytosis and anemia in Gt(ROSA)26Sortm3.1(CAG-Il17a)Awai/Gt(ROSA)26Sor+ mice
|
• there is a substantial increase in the number of granulocytes present in the blood, bone marrow and spleen
|
|
• an upregulated secretion of IL-17A occurs from cells isolated from bone marrow, spleen, thymus, and mesenteric lymph nodes in unstimulated cultures
|
|
• mice show signs of skin inflammation within a few days of birth
|
|
• growth retardation is evident in mice 4-6 days after birth
|
|
• hematocrit is significantly decreased in these mice
|
|
• mice have significantly decreased hemoglobin content
|
|
• is decreased in these mice
|
|
• is decreased in these mice
|
|
• there is a substantial increase in the number of granulocytes present in the blood, bone marrow and spleen
|
|
• mice show signs of skin inflammation within a few days of birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal turpentine-induced inflammatory response
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected mice are born
|
| N |
• mice exhibit normal skin without ulceration, necrosis or inflammation
|
| N |
• brain tissue is normal under MRI and histological examination
|
| N |
• unlike patients with PAPA, mice do not exhibit signs of arthritis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mice exhibit reduced neutrophil infiltration into the skin unlike in control mice
|
|
• 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mice exhibit reduced neutrophil infiltration into the skin unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following withdrawal of doxycycline, peripheral blood parameters are normalized
|
|
• perturbed terminal granulopoiesis with a 2-fold increase in granulo-monocytic progenitors in doxycycline-treated mice
|
|
• increased proliferation and reduced quiescent cells in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• expanded early but inhibited terminal erythropoiesis in doxycycline-treated mice
• splenic stress erythropoiesis with insufficient terminal erythropoiesis doxycycline-treated mice
|
|
• expansion of pre-megakaryoerythroid progenitors in doxycycline-treated mice
|
|
• enhanced monopoiesis with a 3-fold increase in monocyte/dendritic progenitors in doxycycline-treated mice
|
|
• dysmorphic with marginalized hyperlobulated nuclei and reduced cytoplasmic volume in doxycycline-treated mice
|
|
• 7-fold in the bone marrow of doxycycline-treated mice
|
|
• reduction in marrow erythroid precursors in doxycycline-treated mice
|
|
• expansion of pre-erythroid colony-forming unit progenitors and colony forming unit erythroid in doxycycline-treated mice
|
|
• expanded in doxycycline-treated mice
|
|
• expansion of proerythroblasts in doxycycline-treated mice
|
|
• fewer large in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• slightly in doxycycline-treated mice
|
|
• in doxycycline-treated mice
• however, bone marrow cellularity is normal
|
|
• perturbed terminal granulopoiesis with a 2-fold increase in granulo-monocytic progenitors in doxycycline-treated mice
|
|
• enhanced monopoiesis with a 3-fold increase in monocyte/dendritic progenitors in doxycycline-treated mice
|
|
• increased proliferation and reduced quiescent cells in doxycycline-treated mice
|
|
• 7-fold in doxycycline-treated mice
|
|
• perturbed terminal granulopoiesis with a 2-fold increase in granulo-monocytic progenitors in doxycycline-treated mice
|
|
• enhanced monopoiesis with a 3-fold increase in monocyte/dendritic progenitors in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• slightly in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show late-onset retinal dysfunction
|
|
• the a-wave amplitude of the maximal ERG response is decreased at 12 months of age, but not at 3 months of age
• the a-wave amplitude of the photopic ERG responses is decreased more than the b-wave amplitude, indicating more involvement of cone dysfunction
• while a-wave amplitude of the scotopic ERG response is slightly decreased, it is not significant
|
|
• b-wave amplitude of the maximal ERG response is decreased at 12 months of age, but not at 3 months of age
• while b-wave amplitude of the scotopic ERG response is slightly decreased, it is not significant
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cone-rod dystrophy | DOID:0050572 | J:319361 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe hyperglycemia in mice treated with 2 mg/ml doxycycline in the drinking water
doxycycline
• blood glucose levels decline when doxycycline treatment ceases
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals have no obvious defects, have normal fertility and exhibit robust ubiquitous red fluorescence in all tissues and organs examined
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• precursor cells are six times more abundant in the intermediate zone and three times more abundant in the cortical plate compared to mice homozygous for Gt(ROSA)26Sortm1(CAG-Bgeo,-Insc/GFP)Jakn and hemizygous for Tg(Nes-cre)1Wmz
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• antigen producing cells are capable of inducing proliferation of CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch in vitro unlike wild-type cells
|
|
• mice are resistant to direct and passive MOG-induced experimental autoimmune encephalomyelitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• plasma levels of total cholesterol are increased at 10 and 28 weeks of age, indicating hypercholesterolemia that worsens with age
• mice treated with evolocumab, a monoclonal antibody that inhibits human PCSK9, show reduced plasma cholesterol levels
|
|
• plasma levels of LDL cholesterol are increased at 10 and 28 weeks of age
|
| N |
• body weight is normal at 28 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| familial hypercholesterolemia | DOID:13810 |
OMIM:143890 |
J:280156 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• female mice exhibit normal fertility
|
|
|
• at the mid-piece
|
|
|
• immobile epididymis sperm
• however, a small fraction of motile spermatozoa is detected
|
|
|
• at the mid-piece
|
|
|
• immobile epididymis sperm
• however, a small fraction of motile spermatozoa is detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline from birth exhibit a net loss of luminal cells coupled with enhanced differentiation to maintain the pool of differentiated luminal cells compared with wild-type mice
|
|
• mice treated with doxycycline from birth exhibit a net loss of luminal cells coupled with enhanced differentiation to maintain the pool of differentiated luminal cells compared with wild-type mice
|
|
• no mice are recovered at birth when exposed to doxycycline throughout pregnancy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice are recovered at birth when exposed to doxycycline throughout pregnancy
|
|
• mice treated with doxycycline from birth exhibit a net loss of luminal cells coupled with enhanced differentiation to maintain the pool of differentiated luminal cells compared with wild-type mice
|
|
• mice treated with doxycycline from birth exhibit a net loss of luminal cells coupled with enhanced differentiation to maintain the pool of differentiated luminal cells compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced in hepatocytes
• however, supplementation with uridine restores fatty acid beta-oxidation
|
|
• hepatic microvesicular steatosis in untreated mice
• however, supplementation with uridine suppresses steatosis
|
|
• reduced in hepatocytes
• however, supplementation with uridine restores fatty acid beta-oxidation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 72% of mice exhibit decreased splay angles of hindlimb limbs when lifted by the tail compared to 33% of wild-type mice, with earlier onset of 73 days compared to 140 days of age in wild-type mice
|
|
|
• 100% of mice exhibit resting tremor at 247 days of age compared to 6.7% of wild-type mice, with onset at 70 days of age
|
|
• mice exhibit deficits in gripping the beam in the beam walk assay indicating impaired gait
• females show less severe motor defects than males
|
|
|
• a decrease in weight is seen in mice older than P150
|
|
|
• dorsal and ventral columns show decreased numbers of regular axons and increased numbers of irregular axons, indicating axonal dieback and corticospinal degeneration
|
|
|
• dorsal and ventral columns show decreased numbers of regular axons and increased numbers of irregular axons, indicative of axonal dieback
|
|
|
• spinal cord, particularly the lower spinal cord, exhibits a reduction in microtubule stability
|
|
|
• progressive axonal degeneration in the dorsal column
|
|
|
• cortical neurons from P0 mice show a decrease in retrograde movements of axonal lysosomes, with an increase in movements that are halted or stationary
• however, no instantaneous velocity differences in lysosomal movement are seen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary spastic paraplegia 4 | DOID:0110792 |
OMIM:182601 |
J:273408 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numbers are reduced in spleen at young age and become comparable to controls at 6-8 weeks of age
|
|
• numbers are reduced in spleen at young age and become comparable to controls at 6-8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numbers are reduced in spleen at young age and become comparable to controls at 6-8 weeks of age
|
|
• numbers are reduced in spleen at young age and become comparable to controls at 6-8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 of 14 mice exhibit anterior visceral endoderm migration defects compared with wild-type mice
|
|
• 6 of 14 mice exhibit anterior visceral endoderm migration defects compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice exhibit impaired glucose clearance during intraperitoneal glucose tolerance test compared with wild-type mice
|
|
• in doxycycline-treated mice
• however, withdrawal of doxycycline restores glucose levels
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show reduced concentrations of murine amyloid beta40 and amyloid beta42 peptides
• however, concentration of the soluble murine APP alpha is not affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in the cortical and trabecular bone of adult mice treated with doxycycline
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• indistinguishable from wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• heart rate, diastolic and systolic blood pressure, and pulse pressure tend to be slightly elevated but are within normal limits
|
|
• the frontal bone is significantly shorter; however the parietal bone is normal
|
|
• the nasal bone is significantly shorter
|
|
• the frontal bone is significantly shorter; however the parietal bone is normal
|
|
• the nasal bone is significantly shorter
|
|
• first seen at about 1 month of age but transgenics tend to eat slightly more than wild-type mice
|
|
• when placed on a high fat diet male and to a lesser extent female transgenic gain less weight and adipose tissue than wild-type mice
|
|
• when placed on a high fat diet male and to a lesser extent female transgenic gain less weight and adipose tissue than wild-type mice
|
|
• increased 1.5- to 2-fold in both males and females; however, TSH levels were not increased
|
|
• increased 1.5- to 2-fold in both males and females; however, TSH levels were not increased
|
|
• transgenics consume more oxygen per unit body weight compared to wild-type mice on either a normal or high fat diet
|
|
• the frontal bone is significantly shorter; however the parietal bone is normal
|
|
• the nasal bone is significantly shorter
|
|
• the nasal bone is significantly shorter
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:243843 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice live for a median period of 255 days
|
|
• mice exhibit impaired rotarod performance at 6 months of age
|
|
• mice show reduced rearing at 4 and 5 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:243843 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice live for a median period of 289 days
|
|
• mice exhibit impaired rotarod performance at 6 months of age
|
|
• mice show reduced rearing at 4 and 5 months of age
|
|
• mice show reduced number of floor plan moves in the open field at 5 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:243843 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice live for a median period of 204 days
|
|
• mice exhibit impaired rotarod performance at 4 months of age and perform significantly more poorly at 6 months of age compared to the other lines
|
|
• mice show reduced rearing at 4 and 5 months of age, with the greatest reduction compared to the other lines
|
|
• mice show reduced number of floor plan moves in the open field at 5 months of age
|
|
• expression of DARPP-32, a maker of medium spiny neurons, in the striatum is reduced in 4 month old mice
|
|
• striatum and cortex exhibit aggregation of HTT at 4 months of age indicating neuronal pathology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:243843 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice live for a median period of 277 days
|
|
• mice exhibit impaired rotarod performance at 6 months of age
|
|
• mice show reduced rearing at 4 and 5 months of age
|
|
• mice show reduced number of floor plan moves in the open field at 5 months of age
|
|
• striatum and cortex exhibit aggregation of HTT at 4 months of age indicating neuronal pathology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• capsaicin-treated mice exhibit less of a nocifensive response compared with similarly treated wild-type mice
|
|
• following spinal nerve ligation, mice fail to develop tactile hypersensitivity and allodynia unlike similarly treated wild-type mice
|
|
• capsaicin-treated mice exhibit only short-lasting and mild body temperature reduction compared with similarly treated wild-type mice
|
|
• capsaicin-treated mice exhibit only short-lasting and mild body temperature reduction compared with similarly treated wild-type mice
• capsaicin-treated mice exhibit less of a nocifensive response compared with similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• capsaicin infusion after focal induction of Trpv1 expression in subsets of striatal neurons by injection of a lentiviral-cre vector recapitulates contralateral circling behavior at one week post-injection; circling subsides within 15 minutes of capsaicin application
• ipsilateral circling is not observed after capsaicin infusion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after treatment with tamoxifen a significant decrease in adipose tissue deposits is seen
|
|
• a significant increase in mean skeletal muscle fiber diameter is seen in tamoxifen-treated mutants however the number of muscle fibers does not increase
|
|
• after treatment with tamoxifen a significant increase in muscle weight is seen
|
|
• after treatment with tamoxifen a significant increase in skeletal muscle size is seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased neuronal stem cell proliferation following transfection with a cre-expressing adenovirus
|
|
• following transfection with a cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice injected intrabursally with an adenovirus expressing cre recombinase (AdCre) exhibit multifocal sites of epithelial hyperplasia in the ovarian surface epithelium
|
|
|
• mice injected intrabursally with an adenovirus expressing cre recombinase (AdCre) exhibit multifocal sites of epithelial hyperplasia in the ovarian surface epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
• B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells
|
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
• B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells
|
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• injection of TAT-cre results in tumors at the injection site as well as EGFP expression
|
|
• match human clear cell sarcoma tumor histomorphology and immunochemistry
• open chromatin and clear cytoplasm
|
|
• rapid tumor growth after visible detection regardless of latency
|
|
• latency of tumor formation correlated with TAT-cre concentration
|
|
• injection of TAT-cre results in tumors at the injection site as well as EGFP expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
• B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells
|
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
• B cells treated with TAT-cre exhibit increased cell size compared with wild-type cells
|
|
• B cells treated with TAT-cre proliferate in culture unlike wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• astrocytes transfected with a cre-expressing adenovirus exhibit normal proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen starting at P25 show severe failure to thrive and lethality by 3 weeks after tamoxifen injection in most mice
• mice treated with tamoxifen for 4 days starting at P28 to P35 survive to at least 10 months after tamoxifen injection
|
|
• mice exhibit 16% decreased body weight 2 weeks after starting tamoxifen injection, and 24% and 26% decreased weight in males and females, respectively, at 4 weeks postinjection
|
|
• the product of serum TSH and T4 levels, known as T4 resistance index, is increased 5.3-fold in males and 12.4-fold in females after tamoxifen treatment, indicating pituitary resistance to circulating TH levels
|
|
• males exhibit a 3.5-fold increase and females a 9.8-fold increase in TSH 4 weeks after starting tamoxifen injection
|
|
• males exhibit a 2.3-fold increase and females a 1.4-fold increase in rT3 levels 4 weeks after starting tamoxifen injection
• however, T3 levels are similar to controls
|
|
• males exhibit a 1.5-fold increase and females a 1.3-fold increase in T4 levels 4 weeks after starting tamoxifen injection
• liver T4 content is increased by 1.4-fold in both tamoxifen treated males and females
• however, liver T3 content is normal
|
|
• tamoxifen treated mice exhibit a 0.7-fold decrease in T3/T4 ratio, indicating decreased efficiency in generating circulating T3
• cerebral T3 content is decreased 29% and 35% in males and females, respectively, after tamoxifen treatment
• the ratio of liver to serum T3 concentrations is decreased and ratios of T3/T4 content is decreased by 0.6- and 0.7-fold in tamoxifen-treated males and females, respectively, suggesting a decrease of local T3 generation
• however, serum T3 levels and liver T3 content are normal in tamoxifen-treated mice
|
|
• type 1 deiodinase (D1) enzymatic activity is decreased by 69% and 51% in males and females, respectively
• type 2 deiodinase (D2) enzymatic activity is decreased by 47% and 52% in males and females, respectively, after tamoxifen treatment
|
|
• the product of serum TSH and T4 levels, known as T4 resistance index, is increased 5.3-fold in males and 12.4-fold in females after tamoxifen treatment, indicating pituitary resistance to circulating TH levels
|
|
• mice treated with tamoxifen starting at P28 are infertile in matings with control mice for more than 6 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in a small proportion of mice as early as weaning
|
|
• in a small proportion of mice as early as weaning
|
|
• without inflammatory infiltrates in a small proportion of mice
|
|
• without inflammatory infiltrates in a small proportion of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal glomerular development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show a drastic weight loss upon tamoxifen treatment by day 6
|
|
• tamoxifen-treated mice show numerous empty crypts and vacuoles
|
|
• thymus is smaller in tamoxifen-treated mice
|
|
• thymus cellularity is reduced 10-fold in tamoxifen-treated mice
|
|
• most cells in the thymus of tamoxifen-treated mice are CD4-/CD8- double negative, suggesting impaired proliferation capacity of early thymocytes
|
|
• tamoxifen-treated mice exhibit aberrant gut structures, with lamina propria that is detaching from the epithelium and abnormal cell shedding at the top of the villi
|
|
• tamoxifen-treated mice show numerous empty crypts and vacuoles
|
|
• abnormal cell shedding at the top of the villi in tamoxifen-treated mice
|
|
• length of villi is reduced in tamoxifen-treated mice
|
|
• the expansion of splenic T cells in response to CD3 and CD28 stimulation is impaired in tamoxifen-treated mice
• proliferation of sorted splenic B cells upon stimulation with LPS plus IL-4 is reduced in tamoxifen-treated mice
|
|
• thymus is smaller in tamoxifen-treated mice
|
|
• thymus cellularity is reduced 10-fold in tamoxifen-treated mice
|
|
• most cells in the thymus of tamoxifen-treated mice are CD4-/CD8- double negative, suggesting impaired proliferation capacity of early thymocytes
|
|
• red blood cell numbers are reduced in tamoxifen-treated mice
|
|
• hemoglobin is reduced in tamoxifen-treated mice
|
|
• spleen shows a slight increase of CD8+ T cells in tamoxifen-treated mice
|
|
• lymphocyte numbers are reduced in tamoxifen-treated mice
• however, no differences are seen in total number of whole blood cells and neutrophils
|
|
• CD19+CD95+GL-7+ germinal center B cells are almost absent in tamoxifen-treated mice (activated B cells)
• however, proportions of T and B cells in Peyers patches are normal
|
|
• CXCR5+PD-1+ T follicular helper cells are reduced in germinal centers of tamoxifen-treated mice
• percentage of CXCR5+PD-1+ T follicular helper cells is reduced after immunization with NP-CGG
|
|
• tamoxifen-treated mice show a drop in reticulocyte numbers
|
|
• spleen shows a cellularity and composition similar to controls except for a slight increase of CD8+ T cells
|
|
• tamoxifen-treated mice immunized with NP-CGG show a reduction of NP-specific IgM
|
|
• the expansion of splenic T cells in response to CD3 and CD28 stimulation is impaired in tamoxifen-treated mice
• proliferation of sorted splenic B cells upon stimulation with LPS plus IL-4 is reduced in tamoxifen-treated mice
|
|
• thymus is smaller in tamoxifen-treated mice
|
|
• thymus cellularity is reduced 10-fold in tamoxifen-treated mice
|
|
• most cells in the thymus of tamoxifen-treated mice are CD4-/CD8- double negative, suggesting impaired proliferation capacity of early thymocytes
|
|
• spleen shows a slight increase of CD8+ T cells in tamoxifen-treated mice
|
|
• lymphocyte numbers are reduced in tamoxifen-treated mice
• however, no differences are seen in total number of whole blood cells and neutrophils
|
|
• CD19+CD95+GL-7+ germinal center B cells are almost absent in tamoxifen-treated mice (activated B cells)
• however, proportions of T and B cells in Peyers patches are normal
|
|
• CXCR5+PD-1+ T follicular helper cells are reduced in germinal centers of tamoxifen-treated mice
• percentage of CXCR5+PD-1+ T follicular helper cells is reduced after immunization with NP-CGG
|
|
• spleen shows a cellularity and composition similar to controls except for a slight increase of CD8+ T cells
|
|
• tamoxifen-treated mice immunized with NP-CGG show a reduction of NP-specific IgM
|
|
• capacity to mount humoral immune responses against the T-dependent antigen 4-hydroxy-3-nitrophenyl (NP) hapten conjugated to chicken gamma globulin (CGG) is reduced in tamoxifen-treated mice
• spleen histology after immunization with NP-CGG shows a reduction of proliferating B cells
|
|
• the expansion of splenic T cells in response to CD3 and CD28 stimulation is impaired in tamoxifen-treated mice
• proliferation of sorted splenic B cells upon stimulation with LPS plus IL-4 is reduced in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice at 12 months of age show reduced motor coordination on the rotarod, with shorter times before falling
|
|
• 12-month-old mice travel shorter distances in the open field test
|
|
• in the pole test, 12-month-old mice take longer to turn and complete the task, indicating motor deficits and bradykinesia
|
|
• axon guidance-related genes in the midbrain and striatum are dysregulated at 3 and 8 months of age
|
|
• no difference in TH+ neuron counts at 3 and 8 months of age, however by 12 months, months show a reduction in TH+ neurons, indicating progressive loss of dopaminergic neurons
|
|
• dendritic atrophy in the midbrain and striatum is seen in 8-month-old mice
|
|
• mice show deceased dendritic spine density in the midbrain and striatum
|
|
• mice show deceased dendritic length in the midbrain and striatum
|
|
• mice show deceased dendritic branch number in the midbrain and striatum
|
|
• reduction in synaptic protein levels in the midbrain at 3 and 8 months and in the striatum at 8 months, indicating early synaptic dysfunction
|
|
• progressive loss of dopaminergic neurons
|
|
• axon guidance-related genes in the midbrain and striatum are dysregulated at 3 and 8 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:373287 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show longer latency to find the target during the Morris water maze training on day 4
|
|
|
• in the Morris water maze probe test, mice spend less time in the target quadrant
|
|
|
• mice show a reduction in spine density in the hippocampus
|
|
|
• mice show reduced basal synaptic transmission in hippocampal CA1 region
|
|
|
• mice exhibit reduced fEPSP amplitude in hippocampal CA1 region
|
|
|
• mice show compromised LTP, with reduced fEPSP amplitude in hippocampal CA1 region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show reduced freezing time during the contextual part of the fear conditioning test
|
|
|
• mice show longer latency to find the target during the Morris water maze training on day 4
|
|
|
• in the Morris water maze probe test, mice spend less time in the target quadrant
|
|
|
• mice show a reduction in spine density in the hippocampus
|
|
|
• mice show a reduction in post synaptic density in hippocampal CA1
|
|
|
• mice show reduced basal synaptic transmission in hippocampal CA1 region
|
|
|
• mice exhibit reduced fEPSP amplitude in hippocampal CA1 region
|
|
|
• mice show compromised LTP, with reduced fEPSP amplitude in hippocampal CA1 region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• postischemic recovery of +dP/dT and -dP/dT is enhanced in hearts from tamoxifen treated animals as compared to controls
• postischemic recovery of developed pressure is enhanced in hearts from tamoxifen treated animals as compared to controls
|
|
• following tamoxifen administration, ischemia-induced myocardial infarct size is decreased as compared to controls
|
|
• postischemic recovery of +dP/dT and -dP/dT is enhanced in hearts from tamoxifen treated animals as compared to controls
• postischemic recovery of developed pressure is enhanced in hearts from tamoxifen treated animals as compared to controls
|
|
• following tamoxifen administration, ischemia-induced myocardial infarct size is decreased as compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• with maternal injection of high-dose tamoxifen on E7.5 to induce Runx1 reactivation, trasnsplanted, hematopoietic stem cells were isolated and injected into irradiated recipients for a long-term competitive repopulation assay; at E14.5 and E16.5, no signficant differences in reconstitution levels of hematopoietic cells is observed relative to controls
• secondary transplantation of yolk sac-derived bone marrow cells from the primary recipients 12 months following primary transplantation resulted in long-term engraftment
|
|
• exposure of embryos to tamoxifen at E10.5 fails to result in observation of CD45+ definitive hematopoietic cells in the aorta-gonad-mesonephros (AGM) region (no rescue of definitive hematopoiesis), whereas after exposure to tamoxifen at E7.5, a large population of CD45-positive cells are detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of 10 weeks
|
|
• large tumors with metastasis to lymph nodes, livers and/or kidney
|
|
• large tumors with metastasis to lymph nodes, livers and/or kidney
|
|
• large tumors with metastasis to lymph nodes, livers and/or kidney
|
|
• large tumors with metastasis to lymph nodes, livers and/or kidney
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline treatment at E5.5 results in completely penetrant neural tube defects at E12.5
• however, doxycycline treatment at P0.5 results in normal brain development
|
|
• doxycycline treatment at E5.5 results in completely penetrant neural tube defects at E12.5
• however, doxycycline treatment at P0.5 results in normal brain development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hearts show re-expression of fetal cardiac genes
• however, heart development proceeds normally
|
|
• hypertrophic cardiomyocytes are seen in the right ventricle free wall as early as 15 days after birth
• however, aberrant proliferation of or apoptosis of cardiomyocytes is not seen and there is no evidence of increased DNA damage
|
|
• lesions contain degenerating cardiomyocytes
|
|
• hearts at 6 weeks and 6 months of age exhibit white surface scars localized to the subepicardial region of the ventricular free walls; lesions contain degenerating cardiomyocytes and a large degree of collagen deposition indicating focal replacement fibrosis localized to the subepicardial myocardium
|
|
• mice show increased arterial elastance at 6 months of age, which is a measure of arterial load
• the slope of the end-diastolic pressure-volume relationship, which describes diastolic function, is elevated
• however, no effect is seen on the slope of end-systolic pressure-volume relationship, which describes the maximal developed ventricular pressure at any given ventricular volume
|
|
• mice show decreased stroke work at 6 months
|
|
• at 6 months of age
|
|
• at 6 months of age
|
|
• mice exhibit increased dp/dtmax-end-diastolic volume, the relationship between peak rate of pressure rise and EDV, which describes ventricular contractile performance
|
|
• mice show an increase in diastolic myocardial stiffness
|
|
• levels of manganese superoxide dismutase are reduced in scar-containing free-wall right ventricle, but not in non-scarred regions, suggesting impaired response to oxidative stress
• however, only very minor increases in reactive oxygen species are seen, indicating that cardiomyocyte degeneration most likely is not caused by increased oxidative stress
|
|
• hypertrophic cardiomyocytes are seen in the right ventricle free wall as early as 15 days after birth
• however, aberrant proliferation of or apoptosis of cardiomyocytes is not seen and there is no evidence of increased DNA damage
|
|
• lesions contain degenerating cardiomyocytes
|
|
• mice exhibit increased dp/dtmax-end-diastolic volume, the relationship between peak rate of pressure rise and EDV, which describes ventricular contractile performance
|
|
• mice show an increase in diastolic myocardial stiffness
|
|
• cardiomyocyte sarcolemmal integrity is compromised in focal subepicardial areas between 15 and 25 days after birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• increase in total number of colony forming units are found in whole bone marrow cells 4 months post-tamoxifen injection
|
|
|
• expansion of granulocyte and granulocyte-macrophage colony types are found in whole bone marrow cells 4 months post-tamoxifen injection
|
|
|
• decrease in frequency and total number of long term hematopoietic stem cells 4 months post-tamoxifen injection
• decrease in total number of short term hematopoietic stem cells 4 months post-tamoxifen injection
|
|
|
• bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 29% of animals in a 440 day period due to myeloproliferative disorder
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 100% of animals in a 440 day period
• in 33% of mice death is the result of myeloproliferative disorder (MPD)
• in 67% of mice death is the result of mixed myelodysplastic syndrome and myeloproliferative disorder (MDS/MPD)
• bone marrow cells from MDS/MPD or MPD primary transplants transplanted into sublethally irradiated secondary recipients results in 100% lethality due to acute myeloid leukemia (AML)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered a single low dose (4 mg/kg) of tamoxifen to induce cre recombination survive 2 months and then die with multiple abnormalities
• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization
|
|
• mice start to rapidly die after 40 mg/kg tamoxifen administration, with 50% of mortality at day 9
• tamoxifen-administered mice treated with BYL719 are alive after 40 days, however interruption of BYL719 treatment 40 days after tamoxifen-administration leads to rapid death
• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization
|
|
• kidney cysts in tamoxifen-administered mice
|
|
• organomegaly is seen in mice administered a single low dose of tamoxifen
|
|
• vessel abnormalities in tamoxifen-administered mice
• tamoxifen-administered mice treated with BYL719 show normal vessels
|
|
• ecstatic venous channels with a thin endothelial cell lining, surrounded by sparse, erratically distributed vascular smooth muscle cells and a disorganized extracellular matrix are seen in mice administered a low dose of tamoxifen
|
|
• severe vessel dilation in tamoxifen-administered mice
|
|
• intra-abdominal hemorrhages in tamoxifen-administered mice
|
|
• hepatic hemorrhages in tamoxifen-administered mice
|
|
• high number of proliferating cells in affected organs of tamoxifen-administered mice
• however, no changes in apoptosis are seen
• tamoxifen-administered mice treated with BYL719 show a reduction in proliferation
|
|
• loss of spleen microarchitecture integrity in tamoxifen-administered mice
|
|
• loss of spleen microarchitecture integrity in tamoxifen-administered mice
|
|
• expansion of lymphatic vessels in tamoxifen-administered mice
|
|
• mice administered a single low dose of tamoxifen progressively develop asymmetrical overgrowth of extremities, disseminated voluminous tumors and subcutaneous vascular abnormalities
• low-dose tamoxifen administered mice treated with BYL719 show improvement of the overgrowth of extremities, however, withdrawal of BYL719 leads to the development of asymmetric extremity hypertrophy within 4 weeks
|
|
• hepatic hemorrhages in tamoxifen-administered mice
|
|
• severe liver steatosis with vessel disorganization in tamoxifen-administered mice
|
|
• muscle hypertrophy in tamoxifen-administered mice
• mice treated with BYL719 7 days after cre induction show improved muscle hypertrophy
|
|
• low dose tamoxifen-administered mice develop tumors that are lipomatous tumors and severe vascular lesions mixing venous and arterial vessels
• low-dose tamoxifen administered mice treated with BYL719 show reduced and disappearance of visible tumors within 2 weeks
• withdrawal of BYL719 from the low-dose tamoxifen administered mice leads to recurrence of tumors
• low-dose tamoxifen-administered mice treated with rapamycin show no effect on tumor growth
|
|
• kidney cysts in tamoxifen-administered mice
|
|
• fibrosis of the kidney with aberrant vessels in tamoxifen-administered mice
|
|
• scoliosis in tamoxifen-administered mice
• mice treated with BYL719 7 days after cre induction show improved scoliosis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CLOVES syndrome | DOID:0080351 |
OMIM:612918 |
J:264410 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen
|
|
• following treatment with tamoxifen, extramedullary hematopoiesis is observed in spleens
|
|
• following treatment with tamoxifen, mice exhibit erythrocytosis
|
|
• following treatment with tamoxifen, mice exhibit hematocrits close to 80%
|
|
• following treatment with tamoxifen, mice exhibit increased serum erythropoietin levels
|
|
• following treatment with tamoxifen
|
|
• following treatment with tamoxifen
|
|
• following treatment with tamoxifen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematocrit level, erythropoietin level and spleen architecture and weight are similar to mice without cre/ESR1 allele
• the Epas1 allele functions to rescue the erythrocytosis phenotype
|
|
• survival is improved relative to mice carrying the Egln1 null allele, but not to control levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen
|
|
• following treatment with tamoxifen, extramedullary hematopoiesis is observed in spleens
|
|
• following treatment with tamoxifen, mice exhibit hematocrits close to 80%
|
|
• following treatment with tamoxifen, mice exhibit increased serum erythropoietin levels
|
|
• following treatment with tamoxifen
|
|
• following treatment with tamoxifen, however, survival is improved relative to tamoxifen treated Egln1tm2.1Fsl mice alone
|
|
• following treatment with tamoxifen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• following exposure to Dermatophagoides farinae, tamoxifen-treated mice exhibit increased total cells in the bronchioalveolar fluid (5-fold increase in eosinophils and neutrophils), increased goblet cell metaplasia, and increased cytokine secretion (IL4, IL5, IL13, and IFN-gamma) compared with control mice
|
|
• following exposure to Dermatophagoides farinae, tamoxifen-treated mice exhibit increased total cells in the bronchioalveolar fluid (5-fold increase in eosinophils and neutrophils), increased goblet cell metaplasia, and increased cytokine secretion (IL4, IL5, IL13, and IFN-gamma) compared with control mice
|
|
• following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone marrow cells treated with tamoxifen exhibit normal reconstitution capacity hematopoiesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• after tamoxifen treatment of adult mice
|
|
• reduced response to Tnfsf13b in vitro 2 days, and in vivo 3 and 5 days after tamoxifen treatment
• lack of BrdU incorporation after Tnfsf13b induction in vivo 3 and 5 days after tamoxifen treatment
• proliferation in response to anti-Cd40 or anti-Ighm antibody induction
|
|
• in mesenteric lymph nodes and Peyers patches reductions in total B cells occurred as early as days 512 post-tamoxifen treatment, with further reductions occurring through the last time point examined at day 30 post-tamoxifen
|
|
• in mesenteric lymph nodes and Peyers patches
|
|
• severe reduction
|
|
• modest reduction
|
|
• modest reduction
|
|
• reduced response to Tnfsf13b in vitro 2 days, and in vivo 3 and 5 days after tamoxifen treatment
• lack of BrdU incorporation after Tnfsf13b induction in vivo 3 and 5 days after tamoxifen treatment
• proliferation in response to anti-Cd40 or anti-Ighm antibody induction
|
|
• in mesenteric lymph nodes and Peyers patches reductions in total B cells occurred as early as days 512 post-tamoxifen treatment, with further reductions occurring through the last time point examined at day 30 post-tamoxifen
|
|
• in mesenteric lymph nodes and Peyers patches
|
|
• severe reduction
|
|
• modest reduction
|
|
• modest reduction
|
|
• reduced response to Tnfsf13b in vitro 2 days, and in vivo 3 and 5 days after tamoxifen treatment
• lack of BrdU incorporation after Tnfsf13b induction in vivo 3 and 5 days after tamoxifen treatment
• proliferation in response to anti-Cd40 or anti-Ighm antibody induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when bone marrow cells are used to reconstitute lethally irradiated mice, NP-KLH and tamoxifen treated chimeras exhibit a reduction in IgM+ plasma blasts cells compared to when wild-type bone marrow are used
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• greater than 5-fold following tamoxifen-treatment
|
|
• when bone marrow cells are used to reconstitute lethally irradiated mice, NP-KLH and tamoxifen treated chimeras exhibit a reduction in IgM+ plasma blasts cells compared to when wild-type bone marrow are used
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• following tamoxifen-treatment and immunization with NP-KLH
|
|
• greater than 5-fold following tamoxifen-treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal
|
|
• cranial neural crest cells fail to differentiate into osteoblasts unlike in wild-type mice
|
|
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal
|
|
• cranial neural crest cells fail to differentiate into osteoblasts unlike in wild-type mice
|
|
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• serum levels of T. muris-specific IgG1 are decreased compared to controls, IgG2a levels are increased, and total IgE is lower in infected mutants
|
|
• under neutral and Th2 conditions, interferon gamma (Ifng)-producing cells increase in culture compared to controls; under Th1 conditions, there is no change in percentage of Ifng-producing cells
|
|
• Th2 cell differentiation is impaired in culture compared to control CD4 trangenic mice
• under Th2 cell conditions, percentage of T cells expressing Il-4 is lower than in control cultures
• Th2 cytokine production is lower in mice after inoculation with T. muris (helminth)
|
|
• mice are resistant to Leishmania major infection; parasitic replication is controlled and lesions are resolved compared to BALB/c controls
• lymph node cells produce abundant amounts of Ifng
|
|
• mutants are unable to fight infection by T. muris, a helminthic pathogen
• Th2-dependent goblet cell and mucin responses are absent at day 21 after infection
• mice have a higher worm burden than control CD4 transgenic mice; at 32 days after inoculation, infection is still present
|
|
• serum levels of T. muris-specific IgG1 are decreased compared to controls, IgG2a levels are increased, and total IgE is lower in infected mutants
|
|
• under neutral and Th2 conditions, interferon gamma (Ifng)-producing cells increase in culture compared to controls; under Th1 conditions, there is no change in percentage of Ifng-producing cells
|
|
• Th2 cell differentiation is impaired in culture compared to control CD4 trangenic mice
• under Th2 cell conditions, percentage of T cells expressing Il-4 is lower than in control cultures
• Th2 cytokine production is lower in mice after inoculation with T. muris (helminth)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average lifespan is 163.3 days
|
|
• onset or progression of motor neuron degeneration is similar to that seen in mice expressing only Tg(SOD1*G93A)1Gur, with an average onset of disease at 134.2 days
|
|
• mice show impaired performance on the rotarod and in hanging from a grid to a similar extent as seen in mice expressing only Tg(SOD1*G93A)1Gur
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• loss of hair pigmentation in 5 months with irregular deposition of pigment
|
|
• hyperpigmentation at 3 weeks of age that progresses to extremely dark skin by 3 months
|
|
• the trunk dermis contains abundant melanin
|
|
• decreased
|
|
• increased
|
|
• hyperpigmentation within the cranium due to melanocyte overgrowth within the leptomeninges
|
|
• extensive overgrowth of pigmented cells that fills the paces in the cochlea and vestibular system
|
|
• rare melanocytic lesions on the trunk and head
• pigment cells invade the orbital-frontal cortex, cerebellum and medulla oblongata
• one mouse exhibited a large darkly pigmented lesion on the brain surface
• heavily pigmented spinal cord and meninges
• extensive overgrowth of pigmented cells that fills the paces in the cochlea and vestibular system
|
|
• hyperpigmentation at 3 weeks of age that progresses to extremely dark skin by 3 months
• hyperpigmentation extends into the hypodermis
• the trunk dermis contains abundant melanin
• the hair follicle bulbs of the trunk and tail develop dark, ectopic pigmentation
• hyperpigmentation within the cranium due to melanocyte overgrowth within the leptomeninges
• heavily pigmented lymph nodes in the neck and trunk
|
|
• early stages of tail darkening
|
|
• young mice exhibit a mass forming at the anterior of the eye
|
|
• in older mice
|
|
• young mice exhibit thickened uveal tract (iris, ciliary body and choroid) compared with control mice
|
|
• 100% penetrance of uveal melanoma at 3 months
• older mice exhibit bigger tumors that largely fill the vitreous space
|
|
• increased
|
|
• flipping onto the back beginning between month 1 and 3
|
|
• beginning between month 1 and 3
|
|
• at 3 months, most mice exhibit pigmented lesions within the lungs with intravasation into the blood vessels
• heavily pigmented lymph nodes in the neck and trunk
|
|
• 100% penetrance of uveal melanoma at 3 months
• older mice exhibit bigger tumors that largely fill the vitreous space
|
|
• more so than Tg(Mitf-cre)7114Gsb mice
|
|
• heavily pigmented and enlarged in the neck and trunk
|
|
• loss of hair pigmentation in 5 months with irregular deposition of pigment
|
|
• separation of the dermis and epidermis at 3 weeks of age
|
|
• hyperpigmentation at 3 weeks of age that progresses to extremely dark skin by 3 months
|
|
• the trunk dermis contains abundant melanin
|
|
• decreased
|
|
• early stages of tail darkening
|
|
• early stages of tail darkening
|
|
• heavily pigmented spinal cord and meninges
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| uveal melanoma | DOID:6039 |
OMIM:155720 OMIM:606660 OMIM:606661 |
J:225597 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 3 weeks of age, the number of lacZ+ melanocytes in tail scales is normal
|
|
• in older mice, melanin content in the tail scales is reduced compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• melanocytic hyperplasia in tamoxifen treated mice after 2 and 6.5 months
|
|
• 2 months after tamoxifen treatment
|
|
• 2 months after tamoxifen treatment
|
| N |
• tamoxifen-treated mice do not exhibit any behavioral abnormalities
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice
|
|
• large cell carcinoma
|
|
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Pituitary tumor in Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+ Tg(Gfap-cre)2Brn/0 mice
|
• pituitary tumors, mammary gland tumors and primitive neuroectodermal tumors
|
|
• 8 of 16 solid tumors with a latency of a year
• intermediate and anterior lobe
• positive for adrenocorticotropic hormone
|
|
• 8 of 16 solid tumors with a latency of a year
• intermediate and anterior lobe
• positive for adrenocorticotropic hormone
|
|
• 8 of 16 solid tumors with a latency of a year
• intermediate and anterior lobe
• positive for adrenocorticotropic hormone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lethality occurs around E9.5
|
|
• at the 12-14 somite stage no heart is present
|
|
• at E9.5 embryos are very small and some are partially resorbed
|
|
• at E9.5 embryos are very small and some are partially resorbed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E9.5 and E10.5, the cranial neural tube is open dorsally
|
|
• at E9.5 and E10.5, the isthmus (the constriction of the neural tube at the midbrain hindbrain boundary) is absent
|
|
• at E9.5 and E10.5 the brain rostral to the otic vesicle is significantly smaller
|
|
• at E9.5 and E10.5, the cranial neural tube is open dorsally
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Splenomegaly and lack of germinal center formation in Gt(ROSA)26Sortm1(gp80)Eces/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ (left) and Gt(ROSA)26Sortm1(gp80)Eces/Gt(ROSA)26Sor+ Ighg1tm1(cre)Cgn/Ighg1+ mice (right)
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• mice succumb to tumors between 7 and 19 months of age
|
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
|
• in non-immunized and immunized mice
|
|
• NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• mice develop tumors in lymphoid tissues including nasopharynx, armpit, and inguinal region
|
|
• histocytic/dendritic cell sarcoma
|
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
|
• in non-immunized and immunized mice
|
|
• NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
A representative tumor in the nose of a Gt(ROSA)26Sortm1(gp80)Eces/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mouse
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• mice succumb to tumors between 7 and 19 months of age
|
|
• FAS-induced
|
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• immunization fails to promote production of class-switched IgG1 unlike in wild-type mice
|
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
|
• in non-immunized and immunized mice
|
|
• NP-stimulated
|
|
• NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• mice develop tumors in lymphoid tissues including nasopharynx, armpit, and inguinal region
|
|
• histocytic/dendritic cell sarcoma
|
|
• FAS-induced
|
|
• in non-immunized and immunized mice starting at 2 to 3 months of age
|
|
• immunization fails to promote production of class-switched IgG1 unlike in wild-type mice
|
|
• mice exhibit fewer IgG1+ B cells compared to in wild-type mice
|
|
• in the spleen with a slight reduction in the splenic B to T cell ratio
|
|
• in non-immunized and immunized mice
|
|
• NP-stimulated
|
|
• NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• resting and NP-stimulated
|
|
• FAS-induced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Cachexic phenotype of Elavl1tm1Thla/Elavl1tm1Thla Gt(ROSA)26Sortm1(cre/ERT2)Alj/Gt(ROSA)26Sor+ mice observed 4 days after tamoxifen administration
|
• 10 days after tamoxifen treatment
|
|
• following tamoxifen treatment, double positive T cells in the thymus exhibit increased apoptosis and necrosis and decreased proliferation compared with T cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
• 65% 4 days following tamoxifen treatment
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, myeloid cell numbers are decreased compared to in Elavl1tm1Hela homozygotes
|
|
• 4 days following tamoxifen treatment
|
|
• 2-fold following tamoxifen treatment
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, early B cells exhibit increased apoptosis and necrosis and decreased proliferation compared with B cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, early B cells exhibit increased apoptosis and necrosis and decreased proliferation compared with B cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, double positive T cells in the thymus exhibit increased apoptosis and necrosis and decreased proliferation compared with T cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
• bone marrow from tamoxifen-treated mice exhibits decreased myeloerythroid colonies on methylcellulose compared with bone marrow from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, total bone marrow cell numbers and bone marrow cellularity of immature cells are decreased compared to in Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
• 65% 4 days following tamoxifen treatment
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, myeloid cell numbers are decreased compared to in Elavl1tm1Hela homozygotes
|
|
• 4 days following tamoxifen treatment
|
|
• 2-fold following tamoxifen treatment
|
|
• following tamoxifen treatment
|
|
• following tamoxifen treatment, early B cells exhibit increased apoptosis and necrosis and decreased proliferation compared with B cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, early B cells exhibit increased apoptosis and necrosis and decreased proliferation compared with B cells from Elavl1tm1Hela homozygotes
|
|
• 2 to 3 days following tamoxifen treatment, mice exhibit massive villus atrophy and disruption of the epithelial architecture unlike Elavl1tm1Hela homozygotes
|
|
• disrupted following tamoxifen treatment
|
|
• following tamoxifen treatment, goblet cells are lost unlike in Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, proliferation of crypt progenitor cells is decreased while apoptosis is increased unlike in Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, apoptosis of cells in the lamina propria and epithelial cells of the colon is increased compared to in Elavl1tm1Hela homozygotes
|
|
• 2 to 3 days following tamoxifen treatment, mice exhibit massive villus atrophy unlike Elavl1tm1Hela homozygotes
|
|
• 2 to 4 days following tamoxifen treatment
|
|
• 2 to 4 days following tamoxifen treatment the proximal intestine is devoid of food suggesting intestinal blockage
|
|
• following tamoxifen treatment, goblet cells are lost unlike in Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, early B cells exhibit increased apoptosis and necrosis and decreased proliferation compared with B cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, double positive T cells in the thymus exhibit increased apoptosis and necrosis and decreased proliferation compared with T cells from Elavl1tm1Hela homozygotes
|
|
• mouse embryonic fibroblasts treated with 4-hydoxytamoxifen exhibit decreased proliferation compared with similarly treated cells from Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment, proliferation of crypt progenitor cells is decreased while apoptosis is increased unlike in Elavl1tm1Hela homozygotes
|
|
• following tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit cell cycle arrest after 6 days in culture unlike wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
|
|
• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
• treatment with tamoxifen at E10.5 results in subtle to inapparent abnormalities in the cortical hem at E12.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Gt(ROSA)26Sortm2(sb11)Njen TgTn(sb-T2/Onc2)6070Njen mice
|
|
• greater than 90% of moribund mice develop tumors with an average latency of 46 weeks
|
|
• in one mouse
|
|
• in one mouse
|
|
• mice develop hematopoietic tumors including B cell, T cell, and myeloid tumors unlike Gt(ROSA)26Sortm2(sb11)Njen TgTn(sb-T2/Onc2)6070Njen mice that do not develop tumors
|
|
• 3 T cell lymphomas develop
|
|
• 2 myeloid leukemia tumors develop
|
|
• mice develop B cell lymphomas including diffuse large cell lymphomas and follicular lymphomas
• one mouse developed pre-B lymphoma
|
|
• in one mouse
|
|
• in one mouse
|
|
• 3 T cell lymphomas develop
|
|
• 3 T cell lymphomas develop
|
|
• 3 T cell lymphomas develop
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• naive CD4+ T cells release more interferon gamma than controls after cre-mediated deletion of Rnasen induced by tamoxifen treatment
• deficient CD4+ T cells are capable of differentiating into Th1 or Th2 cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) arrest with 2N or 4N DNA content and exhibit reduced S and M phase unlike wild-type MEFs
|
|
• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) exhibit a flattened senescence-like morphology unlike wild-type MEFs
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following injection of tamoxifen at E10.5 most embryonic cells appear to be in prometaphase
|
|
• following injection of tamoxifen at E10.5 embryos show a 4 fold increase in PH3 positive cells in the thymus and lungs compared to controls
|
|
• following injection of tamoxifen at E10.5 about a 3 fold increase in the percentage of apoptotic cells in the thymus and lungs is seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• median survival time of 26 weeks
• castrated mice have a median survival time of 44 weeks
|
|
|
• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points
• tumors regress post-castration but resume growth 24 weeks post-castration
|
|
|
• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points
• tumors regress post-castration but resume growth 24 weeks post-castration
|
|
|
• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points
• tumors regress post-castration but resume growth 24 weeks post-castration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• median survival time of 12.5 weeks
• castrated mice have a median survival time of 24 weeks
|
|
|
• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
• mice do not respond to surgical castration and continue to grow tumors rapidly
• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential
|
|
|
• onset of metastasis occurs as early as 8 weeks and by 12 weeks, 100% of mice develop distant metastatic lesions; metastases to the lung, liver, lymph nodes, and kidney primarily consist of large and small cell neuroendocrine histologies that are AR-negative
|
|
|
• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
• mice do not respond to surgical castration and continue to grow tumors rapidly
• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential
|
|
|
• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
• mice do not respond to surgical castration and continue to grow tumors rapidly
• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate neuroendocrine neoplasm | DOID:2992 | J:307910 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• median survival time of 19 weeks
|
|
|
• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
|
|
|
• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
|
|
|
• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks
• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states
• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology
• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate neuroendocrine neoplasm | DOID:2992 | J:307910 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Internal bleeding and anemia, and hemorrhages in the lung and GI tract in tamoxifen treated Acvrl1tm2.1Spo/Acvrl1tm2.1Spo Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+ mice
|
• adult mice administered with tamoxifen die 9-21 days after a single injection
• tamoxifen treated females show a shorter survival span than males
|
|
• in tamoxifen treated mutants
|
|
• tamoxifen treated mutants show signs of illness such as slow movements, weight loss, pale paws, and low pO2 levels from 8-10 days after tamoxifen injection
|
|
• pulmonary arteries and veins are dilated
• high vascular permeability
|
|
• uterus shows signs of arteriovenous malformations in tamoxifen treated mutants
• mutants bearing excisional wounds on the dorsal skin and ear and treated with tamoxifen form arteriovenous shunts in the blood vessels near the wounds
|
|
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
|
|
• in tamoxifen treated mutants
|
|
• in tamoxifen treated mutants
|
|
• tamoxifen treated mutants show signs of hemorrhages in the lungs
|
|
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
|
|
• tamoxifen treated mutants exhibit darkened feces indicative of the presence of blood
|
|
• tamoxifen treated mutants exhibit reduced hematocrit
|
|
• pulmonary arteries and veins are dilated
• high vascular permeability
|
|
• tamoxifen treated mutants show signs of hemorrhages in the lungs
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary hemorrhagic telangiectasia | DOID:1270 |
OMIM:187300 OMIM:600376 OMIM:615506 |
J:154620 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit very-long-chain fatty acid accumulation in different lipid classes and acylcarnitines
• C26:0 levels are increased 15-fold in brain and 12-fold in spinal cord
• 1-hexacosanoyl-sn-glycero-3-phosophocholine (C26:0-lysoPC) levels are increased 13-fold in the brain, 24-fold in the spinal cord, and 17-fold in the blood
• C26:0-carnitine levels are increased 40-fold in brain, 33-fold in spinal cord, and 16-fold in the blood
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| adrenoleukodystrophy | DOID:10588 |
OMIM:300100 |
J:257393 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection
|
|
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
|
|
|
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
|
|
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
|
|
• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment
|
|
|
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
|
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• 20% of males develop prostate cancer after 4OHT treatment
|
|
|
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
|
|
|
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment
|
|
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
|
|
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline at 1 month of age for 3 days then injected with cardiotoxin into the quadriceps muscle to induce inflammation and muscle damage develop large heterotopic ossification tissue masses
• treatment of cardiotoxin-induced muscle injury with palovarotene diminishes heterotopic ossification formation by more than 80%
|
|
• about 14 days after heterotopic ossification induction by injury in doxycycline treated mice, movement of affected legs is impaired
• treatment with palovarotene of mice with cardiotoxin-induced muscle injury rescues the impaired movement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5, mice exhibit narrowed outflow tract and hypoplastic outlet or subpulmonary conus compared with wild-type mice
|
|
• at E14.5, the right ventricular cavity is smaller than in wild-type mice
• however, the right ventricular muscle wall thickness is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• temporarily delayed at E10.5
|
|
• at E10.5, atrioventricular cushions exhibit rounded endocardial-derived cells that accumulate at the cushion interface and less dense, hypoplastic areas unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• arrested
|
|
• at E10.5, atrioventricular cushions exhibit rounded endocardial-derived cells that accumulate at the cushion interface and less dense, hypoplastic areas unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability (especially chromatid breaks) compared with wild-type cells but at the same level as in Atmtm1Fwa cells
|
|
• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability (especially chromatid breaks) compared with wild-type cells but at the same level as in Atmtm1Fwa cells
|
|
• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability (especially chromatid breaks) compared with wild-type cells but at the same level as in Atmtm1Fwa cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice lack normal goblet cells unlike wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• in the small intestine and colon following tamoxifen treatment
|
|
• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice
|
|
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells unlike in wild-type mice
|
|
• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• tamoxifen-treated mice lack normal goblet cells unlike wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
|
|
• in the small intestine and colon following tamoxifen treatment
|
|
• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer
• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation
• tumors invade the lamina and muscularis propria
• marker analysis indicates that tumors are related to human basal BLCA3 subtype
|
|
• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer
• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation
• tumors invade the lamina and muscularis propria
• marker analysis indicates that tumors are related to human basal BLCA3 subtype
|
|
• 12 of 18 mice develop unilateral or bilateral hydronephrosis as early as 2 weeks after dox treatment due to obstruction of the upper ureter by tumor masses
|
|
• due to bladder tumors in dox treated mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:227748 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show no abnormal phenotype up to 1 year of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die around 6-7 weeks of age due to malnutrition; this is most likely due to difficulty accessing food and water in normal cages due to a rearing defect
• however, when mutants are supplied with hydrated gel packs and crushed pieces of regular chow, all mutants survive beyond 6 months of age, with a majority surviving past 1 year of age
|
|
• mutants are significantly smaller than controls by 5 weeks of age
|
|
• mutants do not gain weight after 4 weeks of age
|
|
• mutants are hunched by 5 weeks of age
|
|
• severe rearing defect as early as 4 weeks of age
• treatment of mutants with L-DOPA alleviates the motor defects
|
|
• mutants are hypoactive by 5 weeks of age
• at 4-5 weeks of age, mutants travel only 68% of the distance traveled by wild-type mice and by 8-11 weeks of age, the distance traveled reduces to 34% of wild-type, indicating an age-dependent decline in locomotive activity
|
|
• beginning at 4-5 weeks, mutants exhibit progressive bradykinesia
• mutants exhibit a decline in the speed of movement with age compared to controls
• mutants spend twice as much time inactive at 6-7 weeks of age as controls and by 8-11 weeks of age, this increases to 6-fold increase in inactive time
|
|
• loss of dopaminergic terminals in the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and 76% reduction by 8-10 weeks
|
|
• mutants exhibit loss of dopaminergic efferents to the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and a 76% reduction by 8-10 weeks of age
• however, projections to the nucleus accumbens and olfactory tubercle are protected and the dopaminergic terminals are moderately preserved at 11-14 weeks
|
|
• dopaminergic neurons remaining have smaller cell bodies and diminished neuronal processes
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
|
|
• retrograde degeneration of substantia nigra pars compacta dopaminergic neurons and to a lesser extent in the mesolimbic pathway
|
|
• progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit, with neuronal loss first seen at 10-12 weeks, when a 52% decrease in TH-positive neurons is seen
• some degeneration is also seen in the mesolimbic pathway, although a lesser extent than in the nigrostriatal circuit
• degeneration of dopaminergic neurons occurs in a stepwise manner, with initial defects at the axon terminals, followed 1-2 months later by degeneration of the cell bodies
|
|
• mutants show decreased mitochondrial transport along nerve processes
|
|
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:188347 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after tamoxifen treatment, the external granule cell layer is much thinner than that of control littermates
• after tamoxifen treatment, the layer is depleted of cycling immature precursors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the precursors to dI3 and dI5 do not leave the ventricular zone at E10.5-E11.5 unlike in controls
• labeled cells do not appear to significantly contribute to the increase in dI2 and dI4 numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E11.5, hearts show deficient second heart field (SHF) contribution to the developing muscular interventricular septum between the right (RV) and left ventricle (LV)
• at E12.5 and E15.5, the interventricular septum has a major deficiency of SHF-derived cells, leading to formation of a bifid cardiac apex
|
|
• E12.5 right ventricle (RV) explant cultures exhibit only non-SHF-derived (mT-labeled) cells migrating from the RV explant by day 6 and very few to no SHF-derived (mG-labeled) cell migration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit very-long-chain fatty acid accumulation in different lipid classes and acylcarnitines
• total C26:0 levels are increased 20-fold in brain, 44-fold in adrenals, 90-fold in testes, 14-fold in lung, 14-fold in liver and 11-fold in kidney
|
|
|
• fewer than the expected number of males are obtained (6% vs the expected 25%), however time is not specified
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 5% of mutants show a hypoplastic pulmonary trunk at E15.5 and E16.5
|
|
• about 30% of mutants exhibit interrupted aortic arch, type b at E15.5 and E16.5
|
|
• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5
|
|
• all mutants exhibit the double outlet right ventricle at E15.5 and E16.5
|
|
• all mutants exhibit a ventricular septal defect at E15.5 and E16.5
|
|
• E17.5 mutants show a smaller frontal bone
|
|
• E17.5 mutants exhibit a smaller mandible
|
|
• E17.5 mutants exhibit a smaller maxilla
|
|
• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5
|
|
• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5
|
|
• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced
|
|
• cell proliferation in the neural crest cell derivatives, aorta and pulmonary trunk walls, is reduced at E12.5
• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the dorsal neural tube, pharyngeal arch regions and outflow tract cushions at E11.5 and no increase in cell death is seen in the dorsal neural tube and outflow tract cushions at E11.5
|
|
• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced
|
|
• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced
|
|
• E17.5 mutants show a smaller frontal bone
|
|
• E17.5 mutants exhibit a smaller mandible
|
|
• E17.5 mutants exhibit a smaller maxilla
|
|
• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced
|
|
• E17.5 mutants show a smaller frontal bone
|
|
• E17.5 mutants exhibit a smaller mandible
|
|
• E17.5 mutants exhibit a smaller maxilla
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 9.5 months, mice exhibit failure in motor coordination during walking and incapability to maintain balance on a rod
|
|
• mice exhibit shorter and more variable strides with more frequent additional steps made by both forepaw and hindpaw compared with wild-type mice
|
|
• and more variable
|
|
• at 6 months in the cerebellum
|
|
• in the cerebellum of aged mice
|
|
• at 6 months in the cerebellum
|
|
• at 6 months in the cerebellum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after doxycycline treatment
|
|
• in the long bones after doxycycline treatment
|
|
• proximal tibial trabecular bone volume/total volume is increased 6.6 fold at 2 months of age after doxycycline treatment
|
|
• markedly increased after doxycycline treatment
|
|
• marked increase in the trabecular bone mass in both primary and secondary ossification centers
|
|
• increased bone formation after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen, cultured tracheal ciliated epithelium exhibits no ciliary activity likely due to a lack of outer dynein arms unlike similarly treated wild-type samples
• however, epithelium morphology and number of ciliated cells are normal following treatment with tamoxifen
|
|
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice
|
|
• after 3 months, tamoxifen-treated mice exhibit absent mucociliary clearance in the nasopharynx and a 50% decreased in the trachea compared with wild-type mice
• after 6 months, 3 of 4 tamoxifen-treated mice exhibit no mucociliary clearance in the trachea while 1 of 4 mice exhibit a substantial reduction in clearance compared with similarly treated wild-type mice
• after 7.5 months, tamoxifen-treated mice exhibit no mucociliary clearance in the trachea compared with similarly treated wild-type mice
|
|
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice
|
| N |
• despite ciliary defects, tamoxifen-treated mice exhibit no evidence hydroencephaly
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| primary ciliary dyskinesia 1 | DOID:0110594 |
OMIM:244400 |
J:155730 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21
|
|
• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 months after tamoxifen treatment, mice develop intestinal disease and eventually die or are sacrificed
|
|
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
|
|
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
|
|
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• sclerotic glomeruli in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• enlarged glomeruli in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• at between 44 and 76 weeks of age, 5 of 29 tamoxifen-treated mice develop sarcomas arising from dermis or muscle connective tissue
|
|
• in tamoxifen-treated mice
|
|
• around the bronchioles in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice die shortly after birth
|
|
• at E18.5, myofibroblasts in the lungs of doxycycline-treated mice exhibit reduced differentiation, as determined by sma+ expression, compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with azoxymethane (AOM) followed by DSS administration show increased distal colorectal cancer compared to controls, with higher average tumor number and increased number of small tumors and proportion of high-grade tumors
|
|
• mice treated with dextran sodium sulfate (DSS) to induce colitis are protected from colitis-induced injury, showing suppression of weight loss and colonic shortening, decreased rectal bleeding rate, better epithelial crypt morphology, and higher proliferation rates and decreased cell death in colonic epithelial tissue compared to controls
|
|
• mice injected with azoxymethane (AOM) followed by DSS administration show increased distal colorectal cancer compared to controls, with higher average tumor number and increased number of small tumors and proportion of high-grade tumors
|
| N |
• mice exhibit normal gastrointestinal development and do not show signs of spontaneous colorectal tumor development up to 8 months of age
|
|
• mice treated with dextran sodium sulfate (DSS) to induce colitis are protected from colitis-induced injury, showing suppression of weight loss and colonic shortening, decreased rectal bleeding rate, better epithelial crypt morphology, and higher proliferation rates and decreased cell death in colonic epithelial tissue compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with dextran sodium sulfate (DSS) to induce colitis show similar colitis-induced injury as controls, with slightly greater weight loss but similar colon shortening and splenic enlargement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal oligodendrocyte myelination
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Gt(ROSA)26Sortm2(sb11)Njen TgTn(sb-T2/Onc2)6070Njen and Gt(ROSA)26Sortm2(sb11)Njen Aicdatm1(cre)Mnz TgTn(sb-T2/Onc2)6070Njen mice
|
|
• mice develop hematopoietic tumors including T cell and erythoid tumors
• tumor latency is 59 days
|
|
• 67% of tumors are T cell lymphomas
|
|
• one mouse exhibited erythroid leukemia
|
|
• 67% of tumors are T cell lymphomas
|
|
• 67% of tumors are T cell lymphomas
|
|
• 67% of tumors are T cell lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 mice develop urinary tract infections
|
|
• in one mouse
|
|
• one mouse exhibited myocyte degeneration
|
|
• one mouse exhibited skin irritation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• massive cell death in the branchial arches without a decrease in cell proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• three weeks after tamoxifen treatment, adult testis size and weight is markedly but not significantly decreased relative to similarly treated controls
|
|
|
• after tamoxifen treatment, GFRalpha1+ cells (corresponding to Asingle~paired spermatogonia in control testis) form Aaligned-like morphologies in adult testes
• c-Kit+ cells aligned more than 32 appear to be absent whereas Aaligned and A1-type spermatogonia are present in control testes, suggesting that c-Kit+ Aaligned spermatogonia fail to differentiate into A1 spermatogonia
|
|
|
• after tamoxifen treatment, most seminiferous tubules lack SCP3+ meiotic cells
|
|
|
• epididymides of tamoxifen-treated adult males are devoid of sperm
|
|
|
• after tamoxifen treatment, adult testes show a marked increase in TUNEL+ apoptotic cells relative to similarly treated controls
|
|
|
• after tamoxifen treatment, adult seminiferous tubules appear atrophied and contain very few spermatocytes; however, germ cells beneath the basement membrane (likely spermatogonia and haploid cells) appear to exist
• most seminiferous tubules lack SCP3+ meiotic cells
|
|
|
• after tamoxifen treatment, adult spermatogenesis is arrested at the c-Kit+ spermatogonia stage
|
|
|
• after tamoxifen treatment, GFRalpha1+ cells (corresponding to Asingle~paired spermatogonia in control testis) form Aaligned-like morphologies in adult testes
• c-Kit+ cells aligned more than 32 appear to be absent whereas Aaligned and A1-type spermatogonia are present in control testes, suggesting that c-Kit+ Aaligned spermatogonia fail to differentiate into A1 spermatogonia
|
|
|
• after tamoxifen treatment, most seminiferous tubules lack SCP3+ meiotic cells
|
|
|
• epididymides of tamoxifen-treated adult males are devoid of sperm
|
|
|
• after tamoxifen treatment, adult testes show a marked increase in TUNEL+ apoptotic cells relative to similarly treated controls
|
|
|
• after tamoxifen treatment, adult testes show a marked increase in TUNEL+ apoptotic cells relative to similarly treated controls
|
|
|
• after tamoxifen treatment, adult seminiferous tubules appear atrophied and contain very few spermatocytes; however, germ cells beneath the basement membrane (likely spermatogonia and haploid cells) appear to exist
• most seminiferous tubules lack SCP3+ meiotic cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hair cells are preserved in the apical, mid, and basal cochlear regions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percentage of polyclonally stimulated apoptotic CD4+ T cells of the parabronchial lymph node from tamoxifen-treated is decreased compared to in control mice
|
|
• the percentage of polyclonally stimulated proliferating CD4+ T cells of the parabronchial lymph node or spleen from tamoxifen-treated is increased compared to in control mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• the percentage of polyclonally stimulated apoptotic CD4+ T cells of the parabronchial lymph node from tamoxifen-treated is decreased compared to in control mice
|
|
• the percentage of polyclonally stimulated proliferating CD4+ T cells of the parabronchial lymph node or spleen from tamoxifen-treated is increased compared to in control mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in the bronchioalveolar following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
• in CD3+/CD4+ T cells from tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
• in CD3+/CD4+ T cells from tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• in restimulated cells from the parabronchial lymph node or splenocytes of tamoxifen-treated Dermatophagoides farinae-exposed mice
• in CD3+/CD4+ T cells from tamoxifen-treated Dermatophagoides farinae-exposed mice
|
|
• following exposure to Dermatophagoides farinae, tamoxifen-treated mice exhibit increased total cells in the bronchioalveolar fluid (5-fold increase in eosinophils and neutrophils), increased goblet cell metaplasia, and increased cytokine secretion (IL4, IL5, IL13, and IFN-gamma) compared with control mice
|
|
• following exposure to Dermatophagoides farinae, tamoxifen-treated mice exhibit increased total cells in the bronchioalveolar fluid (5-fold increase in eosinophils and neutrophils), increased goblet cell metaplasia, and increased cytokine secretion (IL4, IL5, IL13, and IFN-gamma) compared with control mice
|
|
• following exposure to Dermatophagoides farinae in tamoxifen-treated mice
|
|
• the percentage of polyclonally stimulated apoptotic CD4+ T cells of the parabronchial lymph node from tamoxifen-treated is decreased compared to in control mice
|
|
• the percentage of polyclonally stimulated proliferating CD4+ T cells of the parabronchial lymph node or spleen from tamoxifen-treated is increased compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• MigR1-MLL-AF9-transformed and tamoxifen-treated bone marrow cells exhibit impaired initiation and maintenance of leukemic transformation
|
| N |
• tamoxifen-treated mice exhibit normal hematopoiesis, long-term hematopoietic stem cell maintenance, and stem and progenitor cell function
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• greater than 2-fold in tamoxifen-treated mice due to reduced intestinal absorption
• however, kidney function is normal
|
|
• tamoxifen-treated mice fail to exhibit a change in phosphorus in response to nicotinamide unlike similarly treated control mice
|
|
• after 10 week, tamoxifen-treated mice exhibit a 2-fold increase in focal phosphate content compared with similarly treated control mice
|
|
• tamoxifen-treated mice exhibit reduced intestinal absorption of phosphorus compared with similarly treated control mice
• tamoxifen-treated mice fail to exhibit a change in phosphorus in response to nicotinamide unlike similarly treated control mice
• tamoxifen-treated mice exhibit reduced sodium dependent intestinal phosphate transport in the jejunum and ileum compared with similarly treated control mice
• however, tamoxifen-treated mice exhibit normal calcium and sodium-independent phosphate transport
|
|
• in tamoxifen-treated mice
|
|
• greater than 2-fold in tamoxifen-treated mice due to reduced intestinal absorption
• however, kidney function is normal
|
|
• tamoxifen-treated mice develop calcification nodules in the lungs (pulmonary alveolar microlithiasis) unlike similarly treated control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired cell cycle progression in tamoxifen-treated mouse embryonic cells with improper chromosome segregation
|
|
• tamoxifen-treated mouse embryonic cells exhibit improper chromosome segregation
|
|
• in tamoxifen-treated mouse embryonic cells stimulated with serum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average survival is 8.5 +/- 2.3 months
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
• mice show lower lung and liver metastasis from pancreatic ductal adenocarcinoma than in KPCY mice
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture undergo acinar-ductal metaplasia, forming large duct-like structures, indicating induction of acinar-to-ductal transdifferentiation
|
|
• mice with cerulein-induced acute pancreatitis do not show reversion of acinar-ductal metaplasia lesions to normal acinar morphology as in wild-type mice and show complete replacement of pancreatic tissue with fibrosis, infiltration of inflammatory cells, widespread acinar-ductal metaplasia/ pancreatic intraepithelial neoplasia (PanIN) lesions with loss of amylase-expressing acinar tissue, and maintain a small and persistent fraction of apoptotic cells
|
|
• mice with cerulein-induced acute pancreatitis do not show reversion of acinar-ductal metaplasia lesions to normal acinar morphology as in wild-type mice and show complete replacement of pancreatic tissue with fibrosis, infiltration of inflammatory cells, widespread acinar-ductal metaplasia/ pancreatic intraepithelial neoplasia (PanIN) lesions with loss of amylase-expressing acinar tissue, and maintain a small and persistent fraction of apoptotic cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice with cerulein-induced acute pancreatitis show reversion of acinar-ductal metaplasia lesions to normal acinar morphology after 7 days of recovery similarly as in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• average survival is 5.2 +/- 1.2 months
|
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring PanI
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:289183 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 73.3% of 3-month old and 75% of 12-month old mice show normal pancreas
• although 26.7% of 3-month old and 25% of 12-month old mice show rare acinar-ductal metaplasia and low-grade pancreatic intraepithelial neoplasia (PanIN1) lesions, these lesions express TRIM29 due to incomplete recombination of the floxed allele
|
| N |
• all mice are alive at 12 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice with cerulein-induced acute pancreatitis show reversion of acinar-ductal metaplasia lesions to normal acinar morphology after 7 days of recovery as in wild-type mice
|
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture show attenuated KRAStm4Tyj-induced acinar cell transdifferentiation and acinar-ductal metaplasia formation
|
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture show attenuated KRAStm4Tyj-induced acinar cell transdifferentiation and acinar-ductal metaplasia formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5
|
|
• at E12.5
|
|
• rudimentary at E12.5
|
|
• absent at E10.5
|
|
• absence of midbrain structures at E10.5
|
|
• absence of hindbrain structures at E10.5
|
|
• rudimentary at E12.5
|
|
• at E12.5
|
|
• at E12.5
|
|
• at E12.5
|
|
• at E12.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• not developed at E10.5
|
|
• absent at E10.5
|
|
• hypoplastic and malformed
|
|
• hypoplastic and malformed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at P1, mice exhibit a more severe zeugopod phenotypes than in Gt(ROSA)26Sortm5(Etv4/en,-GFP)Amc/Gt(ROSA)26Sor+ Tg(Prrx1-cre)1Cjt mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at P1, digits appear posteriorized comparing relative digit length and phalanx morphology with that of controls Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice
• however, mice have the same number of digits as in Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• less well-formed ectopic cartilaginous elements are observed in the anterior limb unlike in wild-type mice
|
|
• the most anterior digit contains three phalanges instead of the normal two
|
|
• mice have 6 to 7 digits unlike in wild-type mice
• in some cases, the ectopic digit is more centrally located and consists of three phalangeal elements without an additional metacarpal element
|
|
• the most anterior digit contains three phalanges instead of the normal two
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal postnatal growth and survival, and normal juvenile reflexes, including negative geotaxis, surface righting, and forelimb hang
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• focal ventral lobe hyperplasia after 1 year of age in 50% of mice
|
|
|
• focal ventral lobe hyperplasia after 1 year of age in 50% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• maintenance of beta cell is impaired with conversion to delta cell fate
|
|
• maintenance of beta cell is impaired with conversion to delta cell fate
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline
|
|
• epithelial cells of the ocular surface of pups treated with doxycycline (via nursing moms) are hyperplastic and aberrantly desquamated from the conjunctiva
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• the aberrantly desquamated cells within the conjunctival sac are composed of conjunctival epithelial cells and basal cells of stratified epithelia but not corneal epithelial cells, indicating aberrant conjunctival, but not corneal, epithelial cell desquamation
• conjunctival epithelia from pups treated with doxycycline (via nursing moms) exhibit an increase in cell proliferation
|
|
• pups treated with doxycycline (via nursing moms) do not show signs of goblet cell differentiation from the conjunctival epithelium at P9 or P16 unlike controls
|
|
• adult mice administered doxycycline at P90 exhibit loss of goblet cells from the conjunctiva and cellular debris in the conjunctival sac
|
|
• pups from nursing moms administered doxycycline do not exhibit clear conjunctival sacs at P9 as in wild-type pups and instead have a mass of cell debris that is abnormally present in the conjunctival sac, indicating early ocular surface morphogenesis alterations
• adult mice administered doxycycline at P90 exhibit cellular debris in the conjunctival sac
|
|
• pups treated with doxycycline exhibit epidermal metaplasia of corneal epithelium at P16
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline
|
|
• adult mice administered doxycycline at P90, exhibit hair loss one month after doxycycline induction, with random alopecia on the body, including the eyelid within 3 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| keratoconjunctivitis sicca | DOID:12895 | J:194073 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice have a normal pattern of sensory axons in the hind paw
• neuronal overexpression of VEGFB186 significantly protects against neuropathy induced by a high dose of paclitaxel
|
|
• mice have a normal vasculature in the hindlimb
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 days following four paclitaxel injections to the hind paw, about 80% of mice respond to a pinprick stimulus compared to only 20% of wild type; overexpression of Flt1 is protective for sensory neurons to a distal neuropathy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 weeks after tamoxifen-treatment, the total number of cardiomyocytes and percentage of mononucleated cardiomyocytes are increased compared with control mice
|
|
• 2 weeks after tamoxifen-treatment
|
|
• 2 weeks after tamoxifen-treatment
|
|
• increased heart weight to tibia length ratio 2 weeks after tamoxifen treatment
|
|
• cardiomyocytes reenter the cell cycle 8 days after tamoxifen treatment
• increased cardiomyocytes proliferation in tamoxifen treated mice following induction of myocardial infarction
|
|
• following induced myocardial infarction, tamoxifen-treated mice exhibit reduced fibrotic scarring with increased myocardial tissue compared with control mice
• however, mice exhibit ventricular dilation and reduced fractional shortening and ejection fraction 3 weeks after injury
|
|
• 8 days after tamoxifen treatment
|
|
• following induced myocardial infarction, tamoxifen-treated mice exhibit reduced fibrotic scarring with increased myocardial tissue compared with control mice
• however, mice exhibit ventricular dilation and reduced fractional shortening and ejection fraction 3 weeks after injury
|
|
• 2 weeks after tamoxifen-treatment, the total number of cardiomyocytes and percentage of mononucleated cardiomyocytes are increased compared with control mice
|
|
• 2 weeks after tamoxifen-treatment
|
|
• 2 weeks after tamoxifen-treatment
|
|
• cardiomyocytes reenter the cell cycle 8 days after tamoxifen treatment
• increased cardiomyocytes proliferation in tamoxifen treated mice following induction of myocardial infarction
|
|
• 8 days after tamoxifen treatment
|
|
• increased heart weight to tibia length ratio 2 weeks after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice succumb to spontaneous brain tumors
|
|
• tumors are high-grade diffuse gliomas
|
|
• most mice succumb to spontaneous brain tumors
|
|
• tumors are high-grade diffuse gliomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| brain glioma | DOID:0060108 | J:285841 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice succumb to spontaneous brain tumors, with a median survival of 419 days
|
|
• tumors are high-grade diffuse gliomas
• tumors often infiltrate throughout many parts of the brain, particularly in the midbrain and thalamic regions
• tumors express markers of oligodendroglial origin
|
|
• most mice succumb to spontaneous brain tumors, with a median survival of 419 days
|
|
• tumors are high-grade diffuse gliomas
• tumors often infiltrate throughout many parts of the brain, particularly in the midbrain and thalamic regions
• tumors express markers of oligodendroglial origin
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| brain glioma | DOID:0060108 | J:285841 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice develop lethal liver dysplasia
|
|
• doxycycline-treated mice develop lethal liver dysplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice develop lethal liver dysplasia
|
|
• doxycycline-treated mice develop lethal liver dysplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• local bone and marrow tissue in doxycycline-treat mice are replaced with massively enlarged vascular structures (hemangiomas) unlike in wild-type mice
|
| N |
• doxycycline-treat mice exhibit normal bone density, osteoclastic bone remodeling, and bone degradation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pinch injury of adult gastrocnemius muscle results in a 50-fold increase in heterotopic ossification volume compared to mice that have one wild-type allele of Acvr1
|
|
• pinch injury of adult gastrocnemius muscle results in a 50-fold increase in heterotopic ossification volume compared to mice that have one wild-type allele of Acvr1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Gt(ROSA)26Sortm1(tTA,tetO-Mir155)Fjsl/Gt(ROSA)26Sor+ Tg(Nes-cre)1Wmz/0 mice develop disseminated lymphoma
|
• in some mice reared without doxycycline
|
|
• by 5 months in mice reared without doxycycline
|
|
• 10 times in mice reared without doxycycline
|
|
• mice reared without doxycycline die between 3 and 5 months
• however, doxycycline treatment rescues phenotype
|
|
• mice reared without doxycycline develop lymphoid pathology as early as 2 weeks of age
|
|
• in mice reared without doxycycline
|
|
• by 5 months in mice reared without doxycycline
|
|
• 10 times in mice reared without doxycycline
|
|
• in mice reared without doxycycline
|
|
• by 5 months in mice reared without doxycycline
|
|
• in mice reared without doxycycline
• however, doxycycline treatment rescues phenotype
|
|
• severe hind limb paresis in some mice reared without doxycycline
• however, doxycycline treatment rescues phenotype
|
|
• following treatment with doxycycline partially due to apoptosis in mice reared without doxycycline
|
|
• in most mice reared without doxycycline
• however, doxycycline treatment rescues phenotype
|
|
• scruffy in mice reared without doxycycline
• however, doxycycline treatment rescues phenotype
|
|
• in some mice reared without doxycycline
|
| N |
• doxycycline-treated mice exhibit normal brain morphology
|
|
• by 5 months in mice reared without doxycycline
• however, doxycycline treatment rescues phenotype
|
|
• tumor cells from mice reared without doxycycline exhibit increased apoptosis following doxycycline treatment
|
|
• in mice reared without doxycycline
|
|
• by 5 months in mice reared without doxycycline
|
|
• 10 times in mice reared without doxycycline
|
|
• in mice reared without doxycycline
|
|
• in mice reared without doxycycline
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lymphoma | DOID:0060058 | J:185598 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disorganized tongue muscle fibers at E14
|
|
• die around the time of birth
|
|
• poor colonization of the outflow tract by cardiac neural crest cells at E10.5
|
|
• poor colonization of the outflow tract by cardiac neural crest cells at E10.5
• at E11 the outflow tract has a lower density of cardiac neural crest cells and these cells are disorganized
• however, septation occurs normally
|
|
• in some embryos
|
|
• malformed outflow tract valves in 90% of mice at E12
|
|
• poor colonization of the outflow tract by cardiac neural crest cells at E10.5
|
|
• smaller and misshapen
|
|
• less affected compared to germline null mice
|
|
• at E17
|
|
• fail to grow and close over the eye bulb at E17
|
|
• boundary of ossification is abnormal
|
|
• severely malformed
|
|
• poorly developed
|
|
• severely malformed palatal cartilage in 33% of mice with less severe malformations in the remaining 67% of mice
• otic capsule cartilage is absent at E16 in 33% of mice and reduced in 66% of mice
|
|
• cartilage is absent at E16 in 33% of mice and reduced in 66% of mice
|
|
• boundary of ossification is abnormal
|
|
• severely malformed
|
|
• poorly developed
|
|
• severely malformed cartilage in 33% of mice with less severe malformations in the remaining 67% of mice
|
|
• disorganized tongue muscle fibers at E14
|
|
• small tongue at E14
|
|
• severely malformed cartilage in 33% of mice with less severe malformations in the remaining 67% of mice
|
|
• disorganized tongue muscle fibers at E14
|
|
• small tongue at E14
|
|
• severely malformed
|
|
• poorly developed
|
|
• severely malformed cartilage in 33% of mice with less severe malformations in the remaining 67% of mice
|
|
• disorganized tongue muscle fibers at E14
|
|
• small tongue at E14
|
|
• poor colonization of the outflow tract by cardiac neural crest cells at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit variable preaxial forelimb polydactyly
|
|
• limb truncation
|
|
• mice exhibit reduced mineralization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced lipogenesis in brown adipocytes
|
|
• on standard chow and a high-fat diet
|
|
• less hypertrophy when fed a high-fat diet than in control mice
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on a high-fat diet
|
|
• on standard chow and a high-fat diet
|
|
• on standard chow and a high-fat diet
|
| N |
• mice exhibit normal food intake and physical activity when fed standard chow or a high-fat diet
|
|
• increased uncoupled respiration in brown adipose tissue mitochondria
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed normal chow exhibit normal epididymal white adipose tissue weight
|
| N |
• mice fed normal chow exhibit normal food intake and locomotor activity
|
| N |
• mice fed normal chow exhibit normal susceptibility to age-associated weight gain and body length
|
| N |
• mice fed normal chow exhibit normal oxygen consumption and rectal temperature
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal hypothalamus-pituitary-adrenal and hypothalamus-pituitary-thyroid axes
|
|
|
• noradrenaline turnover in the white adipose tissue is increased in male mice compared to in control mice
• however, turnover in skeletal muscle is normal
|
|
• mice tend to be cold-resistant for short-term exposure compared with control mice
• however, mice fed a high fat high sugar diet exhibit normal cold resistance
|
|
• tend
|
|
|
• male mice fed normal chow exhibit increased energy expenditure suggested by a tend toward higher oxygen consumption and lower locomotor activity compared with control mice
• however, mice fed a high fat high sugar diet exhibit normal energy expenditure
|
|
|
• trend in male mice fed normal chow
|
|
• mice exhibit improved leptin sensitivity compared with control mice
|
| N |
• male and female mice fed normal chow exhibit normal body length
• mice fed a high fat high sugar diet exhibit normal weight gain
|
|
|
• in male, but not female, mice fed normal chow
|
|
|
• in male, but not female, mice fed normal chow
• however, mice fed a high fat high sugar diet exhibit normal adiposity
|
|
|
• in male mice fed normal chow
|
|
|
• noradrenaline turnover in the white adipose tissue is increased in male mice compared to in control mice
• however, turnover in skeletal muscle is normal
|
| N |
• female and male mice exhibit normal food intake
|
|
|
• trend in male mice fed normal chow
• however, mice fed a high fat high sugar diet exhibit normal locomotion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal body length
• female and male mice fed a high fat high sugar diet exhibit normal body weight
|
|
|
• female mice exhibit a tend toward increased body weight
|
|
|
• in male mice fed normal chow
|
| N |
• mice fed normal chow or a high fat high sugar diet exhibit normal locomotor activity
|
|
|
• in male mice fed normal chow
|
|
|
• in female mice fed normal chow
|
| N |
• mice fed normal chow exhibit normal energy expenditure, plasma T4 levels, fasting-induced lipolysis and rectal temperature
• mice fed a high fat high sugar diet exhibit normal energy expenditure and cold tolerance
|
|
• mice exhibit improved leptin sensitivity compared with control mice
|
| N |
• mice fed normal chow or a high fat high sugar diet exhibit normal adiposity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed normal chow exhibit normal epididymal white adipose tissue weight
|
| N |
• mice fed normal chow exhibit normal food intake and locomotor activity
|
| N |
• mice fed normal chow exhibit normal susceptibility to age-associated weight gain and body length
|
| N |
• mice fed normal chow exhibit normal oxygen consumption
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all tamoxifen-treated mice develop sarcomas of the skin or muscle connective tissue after 10 to 19 weeks
|
|
• 2 tamoxifen-treated mice develop large intestinal tumors resembling undifferentiated fibrosarcomas
|
|
• tamoxifen-treated mice develop muscle fibrosis at 10 to 19 weeks of age
|
|
• tamoxifen-treated mice develop skin fibrosis at 10 to 19 weeks of age
|
|
• after 15 weeks, tamoxifen-treated mice exhibit intestinal fibrosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• rhombomere 1 is diminished with only a small domain adjacent to axonal bundles connected to the trigeminal ganglia
• dorsal rhombomere 1 is severely depleted but the ventral portion is less severely affected
|
|
• substantial depletion of the En1 lineage derived mesencephalon at E12.5
• dorsal mesencephalon is severely depleted but the ventral portion is less severely affected
|
|
• severe truncation of the lateral anterior hindbrain
|
|
• aberrantly patterned whisker fields innervated by serotonergic neurons
|
|
• absence of LMX1a+ progenitors throughout the medial-lateral extent of the ventral mesencephalon and decreased numbers in the ventral diencephalon
|
|
• only a small disorganized cohort of TH+ MbDA neurons remain at E8.5
|
|
• rhombomere 1 is diminished with only a small domain adjacent to axonal bundles connected to the trigeminal ganglia
• dorsal rhombomere 1 is severely depleted but the ventral portion is less severely affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the brain and liver of tamoxifen treated mice compared with control mice but not as severe as in mice also lacking the Kdr null allele
• some small focal areas in the retina in tamoxifen-treated mice relative to mice lacking the Kdr null allele
• however, angiogenesis in the heart is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced cellularity in tamoxifen-treated mice from P4
• however, mice recover one month after the last tamoxifen application
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• most mice develop metastases which are numerous and widespread in many different sites, including the lymph nodes, diaphragm, lungs, and liver
• all mice exhibit peritoneal disseminated tumor cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
• mice exhibit a shorter survival than KPCT mice
|
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bone marrow cells used in a transplantation experiment following tamoxifen-induction produce NOTCH1-induced tumors that are resistant to 6-mercaptopurine chemotherapy unlike control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vascular smooth muscle cell abnormalities in Gt(ROSA)26Sortm3(NOTCH3*R1031C)Sat/Gt(ROSA)26Sor+ Tg(Tagln-cre)1Her/0 and Gt(ROSA)26Sortm2(NOTCH3*C455R)Sat/Gt(ROSA)26Sor+ Notch3Gt(PST033)Byg/Notch3Gt(PST033)Byg Tg(Tagln-cre)1Her/0 mice
|
• vascular smooth muscle cell abnormalities with intracellular inclusions are seen at 6 months of age
|
|
• increased susceptibility to ischemic injury seen in Notch3 null mice is not rescued by expression of the mutant human NOTCH3
|
|
• vascular smooth muscle cell abnormalities with intracellular inclusions are seen at 6 months of age
|
|
• increased susceptibility to ischemic injury seen in Notch3 null mice is not rescued by expression of the mutant human NOTCH3
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CADASIL 1 | DOID:0111035 |
OMIM:125310 |
J:171887 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following tamoxifen-treatment, injury-induced myogenesis and satellite cell characteristics are normal
|
|
• in culture, tamoxifen-treated P0 myoblasts exhibit defective expansive and myogenic potentials compared with control Pax7tm2.1(cre/ERT2)Fan heterozygous myoblasts
• however, myoblasts from tamoxifen-treated adults exhibit normal expansive and myogenic potentials
|
|
• following tamoxifen treatment between P7 and P11, regeneration is severely compromised compared to in control Pax7tm2.1(cre/ERT2)Fan heterozygotes
• however, following tamoxifen treatment between P14 to P18 and P21 to P25 regeneration capacity gradually increased to levels in control Pax7tm2.1(cre/ERT2)Fan heterozygotes
• following tamoxifen treatment, myofibers continue to be incorporated into a regenerating muscle beyond P31 longer than in control Pax7tm2.1(cre/ERT2)Fan heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• increased susceptibility to ischemic injury seen in Notch3 null mice is rescued by expression of the human NOTCH3
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased susceptibility to ischemic injury seen in Notch3 null mice is not rescued by expression of the mutant human NOTCH3 at 1 year of age but is rescued at 3 to 6 months of age
|
|
• increased susceptibility to ischemic injury seen in Notch3 null mice is not rescued by expression of the mutant human NOTCH3 at 1 year of age but is rescued at 3 to 6 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CADASIL 1 | DOID:0111035 |
OMIM:125310 |
J:171887 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased body weight before P56
|
| N |
• mice do not show overt motor abnormalities
|
| N |
• mice show normal survival
|
| N |
• brain morphology and size appear normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not
|
|
• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6
|
|
• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when cre expression is induced with a tamoxifen-containing diet (400 mg/kg of chow), mice die by day 9 post-introduction of tamoxifen
|
|
• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not
|
|
• mice show a cumulative loss of body weight compared to controls following cre induction, but energy intake (cumulative food intake) is similar to controls
|
| N |
• without induction of cre by tamoxifen treatment, animals are indistinguishable from controls
|
|
• increased fat oxidation after induction is basis for increased weight loss
|
|
• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6
|
|
• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
|
|
• increased fat oxidation after induction is basis for increased weight loss
|
|
• energy intake on day 7 is significantly higher than on day 1 after cre induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Thymic aplasia, nasal malformations, and eye, pharyngeal and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Foxg1tm1(cre)Skm/Foxg1+ mice and microcephaly, ocular and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Tg(Pax2-cre)1Akg/0 mice
|
• hypoplastic to varying degrees, but enlarged in two instances
|
|
• fusion plates are not joined at E12.25
• however, they have partially recovered by E14.5
|
|
• enlarged at E14.5
|
|
• enlarged at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal heart development at E14.5
|
| N |
• mice do not exhibit any morphological defects in the inner ear
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cell but not T cell numbers are reduced in the bone marrow and spleen to 65% and 50% of control, respectively
• B cell turn over is also increased in double mutants
|
|
• B cell but not T cell numbers are reduced in the bone marrow and spleen to 65% and 50% of control, respectively
• B cell turn over is also increased in double mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• absence of Bcl10 expression rescues the early lethality seen in mutant mice wild-type for Bcl10
|
| N |
• absence of Bcl10 expression rescues the pathological B-cell activation, differentiation, and malignant proliferation seen in mutant mice wild-type for Bcl10
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die by P6
|
|
• blastoid cells that infiltrate solid organs are seen indicating high-grade lymphoma
• blastoid B cells express low levels of IL7 or CD25 indicating the disease does not resemble acute B-cell lineage leukemia
|
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
|
• spleens contain homogenous populations of large cells with prominent nucleoli and high proliferation indices
|
|
• massive
|
|
• high proliferation indices
|
|
• recombined B cells exhibit an activated phenotype with high CD80 and Sca-1 expression and elevated CD43 levels
|
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
|
• massive reduction in the B220+ IgM- compartment in the bone marrow indicating infiltration by peripheral blastoid B cells
|
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
|
• B cells in the spleen and bone marrow are CD138+ B220int or CD138+ B220low indicating these consist of plasmablasts and plasma cells
|
|
• spleens contain homogenous populations of large cells with prominent nucleoli and high proliferation indices
|
|
• massive
|
|
• high proliferation indices
|
|
• recombined B cells exhibit an activated phenotype with high CD80 and Sca-1 expression and elevated CD43 levels
|
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
|
• B cells proliferate vigorously in the absence of any specific B cell survival or mitogenic factors for at least 10 days in culture
• high proliferation indices in the spleen
|
|
• massive
|
|
• high proliferation indices
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| diffuse large B-cell lymphoma | DOID:0050745 | J:228288 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Enlarged spleen and solid organ infiltration with abnormally proliferating T cells in Gt(ROSA)26Sortm1(ITK/SYK)Jrld/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mice
|
• mice develop lethal wasting and die by 60 weeks of age unlike wild-type mice
|
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• at 50 weeks
|
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• at 50 weeks
|
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• at 50 weeks
|
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• mice develop infiltrating lymphocytes into multiple organs unlike in wild-type mice
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
• lymphomas consists of enlarged, activated, and highly proliferative T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• absence of Malt1 expression rescues the early lethality seen in mutant mice wild-type for Malt1
|
| N |
• absence of Malt1 expression rescues the pathological B-cell activation, differentiation, and malignant proliferation seen in mutant mice wild-type for Malt1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• of follicular II B cells in the spleen
|
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
|
• reduced development with reduced number of class switched IgG1 B cells in the Peyer's patch
|
|
• impaired marginal zone B cell differentiation
|
|
• reduced number of class switched IgG1 B cells in the Peyer's patch
• almost complete block of class switch to IgA, IgG1, IgG2b and IgG3
|
|
• in the spleen
|
|
• in the spleen
|
|
• increased percent
|
|
• absence of the marginal zone B cells peripheral to follicles in the spleen
|
|
• in the spleen
|
|
• increased percentage in the peritoneal cavity
|
|
• decreased follicular II B cell compartment and increase in follicular I B cell numbers in the spleen
|
|
• following immunization with NP-CG antigen
• however, levels in naive mice are normal
|
|
• following immunization with NP-CG antigen
|
|
• in naive mice and following immunization with NP-Ficoll
|
|
• in naive mice and following immunization with NP-Ficoll
• however, levels are normal following immunization with NP-CG antigen
|
|
• of follicular II B cells in the spleen
|
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
|
• of follicular II B cells in the spleen
|
|
• of follicular I and follicular II B cells in the spleen
• of B cells stimulated with LPS, CpG or anti-IgM F(ab)'2 in vivo or in vitro
|
|
• impaired marginal zone B cell differentiation
|
|
• reduced number of class switched IgG1 B cells in the Peyer's patch
• almost complete block of class switch to IgA, IgG1, IgG2b and IgG3
|
|
• in the spleen
|
|
• in the spleen
|
|
• increased percent
|
|
• absence of the marginal zone B cells peripheral to follicles in the spleen
|
|
• in the spleen
|
|
• increased percentage in the peritoneal cavity
|
|
• decreased follicular II B cell compartment and increase in follicular I B cell numbers in the spleen
|
|
• following immunization with NP-CG antigen
• however, levels in naive mice are normal
|
|
• following immunization with NP-CG antigen
|
|
• in naive mice and following immunization with NP-Ficoll
|
|
• in naive mice and following immunization with NP-Ficoll
• however, levels are normal following immunization with NP-CG antigen
|
|
• reduced development with reduced number of class switched IgG1 B cells in the Peyer's patch
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no parasympathetic precursors are detectable at E12.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• consistent with the liver damage seen, ALT levels are increased 5-7 fold
|
|
• consistent with the liver damage seen, AST levels are increased 5-7 fold
|
|
• increased liver cell death is seen in 6 week old double hemizygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-fold decrease in ventral oligodendrogenesis in the prepontine (rhombomere 2- and 3-derived) and pontine (rhombomere 4-derived) territories compared with controls
• however, migration of oligodendrite progenitor cells is normal
|
|
• decrease in ventral oligodendrogenesis in the prepontine (rhombomere 2- and 3-derived) and pontine (rhombomere 4-derived) territories at E13.5 due to reduced proliferation
• however, ventricular progenitors are recovered following additional cell cycle before differentiation
|
|
• decrease in ventral oligodendrogenesis in the prepontine (rhombomere 2- and 3-derived) and pontine (rhombomere 4-derived) territories at E13.5 due to reduced proliferation
• however, ventricular progenitors are recovered following additional cell cycle before differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants die between P12 and P14
|
|
• double mutants develop hindlimb weakness around P8-10
|
|
• around P8-10 double mutants begin to lose weight
|
|
• from P0 to P14, no oligodendrocytes can be detected in double mutants
|
|
• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen
|
|
• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen
|
|
• from P0 to P14, no oligodendrocytes can be detected in double mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in culture primary kidney epithelial cells show a delay in the formation of mature cell junctions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants are born alive but die within the first day
|
|
• at E14.5, large numbers of apoptotic cells can be seen in the cre-expressing neuronal layer, in contrast no apoptotic cells are seen in controls
• at E16.5, the cortex is filled with many apoptotic cells and at E18.5 the cortex is highly degenerated and thin with abnormal layering and a wavelike structure
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in pro-B, pre-B and immature B cells of tamoxifen-treated mice
• however, apoptosis is rescued by exogenous Bcl2 or Mdm2 and Bcl2
|
|
• in the bone marrow of tamoxifen-treated mice
|
|
• few early T cell progenitors in the thymus of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• reduced 7-fold in tamoxifen-treated mice
|
|
• in the bone marrow of tamoxifen-treated mice
• however, the number of B cells in the spleen, lymph node and peripheral blood is normal
|
|
• to one-fifth of wild-type levels in the bone marrow of tamoxifen-treated mice
|
|
• in the bone marrow of tamoxifen-treated mice
|
|
• reduced LSK and lymphoid-primed multipotent progenitors in tamoxifen-treated mice
|
|
• tamoxifen-treated LSK cells exhibit a complete loss of lymphoid development
|
|
• in pro-B, pre-B and immature B cells of tamoxifen-treated mice
• however, apoptosis is rescued by exogenous Bcl2 or Mdm2 and Bcl2
|
|
• in pro-B, pre-B and immature B cells of tamoxifen-treated mice
• however, apoptosis is rescued by exogenous Bcl2 or Mdm2 and Bcl2
|
|
• complete loss of lymphoid development in tamoxifen-treated bone marrow cells is cell autonomous
|
|
• in the bone marrow of tamoxifen-treated mice
|
|
• few early T cell progenitors in the thymus of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the bone marrow of tamoxifen-treated mice
• however, the number of B cells in the spleen, lymph node and peripheral blood is normal
|
|
• to one-fifth of wild-type levels in the bone marrow of tamoxifen-treated mice
|
|
• in the bone marrow of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decrease in the number of V1 neurons in the spinal cord
|
|
• significant increase in the length of both step cycle period and motor neuron burst duration during fictive locomotion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• early B cell development is rescued in tamoxifen treated mice
|
|
• reduced LSK and lymphoid-primed multipotent progenitors in tamoxifen-treated mice
|
|
• tamoxifen-treated LSK cells exhibit a complete loss of lymphoid development
|
| N |
• early B cell development is rescued in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hypoxic primary tubular epithelial cells from doxycycline treated mice fails to migrate unlike similarly treated cells from Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1(rtTA)Awu/Gt(ROSA)26Sor+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• after ureteral ligation, mice exhibit reduced fibrosis and inflammation compared with similarly treated Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+ mice
|
|
|
• after ureteral ligation, mice exhibit reduced fibrosis and inflammation compared with similarly treated Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+ mice
|
|
|
• hypoxic primary tubular epithelial cells fails to undergo an epithelial to mesenchyme transition unlike similarly treated cells from Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+ mice
|
|
|
• after ureteral ligation, mice exhibit reduced fibrosis and inflammation compared with similarly treated Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+ mice
|
|
|
• after ureteral ligation, mice exhibit reduced fibrosis and inflammation compared with similarly treated Hif1atm3Rsjo/Hif1atm3Rsjo Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• axons of OLFR151 expressing olfactory sensory neurons appear to co-converge and coalesce in glomerular formation correctly despite G-protein disruption during development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer cortical neurons expressing Satb2
• however, the number of Foxp1 and total neuron numbers are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of Cajal-Retzius cells in the cortical marginal zone is reduced by 72% at P0
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of Cajal-Retzius cells in the cortical marginal zone is reduced by 35% at P0
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal proliferation of YFP+ acinar cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes slow movement
|
|
• adults injected with tamoxifen for 3 days develop arteriovenous malformations in AAV-VEGF-induced brain angiogenic foci 8 weeks after induction, with lesions consisting of enlarged vessels
(J:212952)
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show the presence of arteriovenous (AV) shunts
(J:227170)
|
|
• macrophages and microhemorrhage are seen around dysplastic vessels of AAV-VEGF injected, tamoxifen treated mice in the brain
|
|
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show dilated and torturous vessels and the presence of arteriovenous (AV) shunts
(J:227170)
• however, blood vessels away from the wound have normal morphology
(J:227170)
|
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes diarrhea
|
|
• tamoxifen treated adults develop arteriovenous malformations around the ear-tag wound
(J:212952)
• areas of wounds in mid-dorsum and ear of tamoxifen-injected mice show dilated and torturous vessels and the presence of arteriovenous (AV) shunts
(J:227170)
• however, blood vessels away from the wound have normal morphology
(J:227170)
|
|
• mice display signs of illness in 3-4 days after the first tamoxifen injection which includes dehydration
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary hemorrhagic telangiectasia | DOID:1270 |
OMIM:187300 OMIM:600376 OMIM:615506 |
J:212952 , J:227170 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of Cajal-Retzius cells in the cortical marginal zone is reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants die between P12 and P14
|
|
• double mutants develop hindlimb weakness around P8-10
|
|
• around P8-10 double mutants begin to lose weight
|
|
• from P0 to P14, no oligodendrocytes can be detected in double mutants
|
|
• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen
|
|
• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen
|
|
• from P0 to P14, no oligodendrocytes can be detected in double mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of Cajal-Retzius cells (CRc) in the cortical marginal zone is reduced by 84% at P0
• nearly all CRc in the hippocampal formation are ablated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 45 days of tamoxifen treatment, mice exhibit visible tumors in the tails and ears unlike similarly treated wild-type mice
• 90 days after tamoxifen treatment, mice exhibit fully developed basal cell carcinomas (BCC) that are not invasive or aggressive over time
• BCCs likely originate from the outer root sheath of the hair follicle based on antibody staining
|
|
• after 200 days of tamoxifen treatment tumors are smaller than fully developed basal cell carcinomas and exhibit decreased proliferation indicating regression
|
|
• after 45 days of tamoxifen treatment, mice exhibit visible tumors in the tails and ears unlike similarly treated wild-type mice
• 90 days after tamoxifen treatment, mice exhibit fully developed basal cell carcinomas (BCC) that are not invasive or aggressive over time
• BCCs likely originate from the outer root sheath of the hair follicle based on antibody staining
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| basal cell carcinoma | DOID:2513 | J:158915 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal pancreatic ductal morphology and pancreata mass
|
|
• tamoxifen-treated mice exhibit a decrease in YFP+ centroacinar cells compared with control mice
|
|
• tamoxifen-treated mice exhibit an increase in YFP+ acinar cells compared with control mice
|
|
• tamoxifen-treated mice exhibit a rapid transformation of YFP+ centroacinar cells into acinar cells compared with control mice
• however, tamoxifen-treated mice exhibit normal centroacinar and acinar cells proliferation and apoptosis
|
|
• tamoxifen-treated mice exhibit a decrease in YFP+ centroacinar cells compared with control mice
|
|
• tamoxifen-treated mice exhibit an increase in YFP+ acinar cells compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival in mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks is 326 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival in mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks is 205 days
• median survival in mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks and 1 umol CTX is 171 days compared with 338 days for control mice
• median survival in mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks is 160 days compared with 228 days for control mice
|
|
• mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks or intramuscular treatment 50 ug tamoxifen at 2 weeks exhibit rare follicular tumors on the trunk and paws
|
|
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen and 1 umol CTX at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks unlike control mice
|
|
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen and 1 umol CTX at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks unlike control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival in mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks is 205 days
• median survival in mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks and 1 umol CTX is 171 days compared with 338 days for control mice
• median survival in mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks is 160 days compared with 228 days for control mice
|
|
• 19 days after the first injection of tamoxifen, the thymus has lost its regular morphology and the cortex is no longer distinguishable from the medulla
|
|
• 15 days after the first injection of tamoxifen, thymus cellularity is decreased by 13-fold
|
|
• 19 days after the first injection of tamoxifen, the DN1 population is overrepresented while the DN2 and DN3 populations are underrepresented
• however, the DN4 population is stable after tamoxifen treatment
|
|
• 19 days after the first injection of tamoxifen, the relative number of immature double positive cells is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, the number of neutrophilic granulocytes is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, circulating B220high, IgD+ B cells are increased compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, mature B cells are overrepresented in the spleen compared to in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the relative number of mature single positive cells is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, total lymphocyte fraction in the bone marrow is only slightly decreased compared to in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the number of double positive cells is almost depleted compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, the number of B220+ B cells in the spleen is reduced (4.71+/-2.33% compared to 13.98+/-3.74% in Ptch1tm1Jwnd control mice)
|
|
• following treatment with tamoxifen, CD43+ B cells are almost completely absent and fraction I and II immature B cells are decreased in the bone marrow compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, the number of T1 transitional B cells is reduced in the spleen compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, bone marrow B220low pre-B cells are lower than in Ptch1tm1Jwnd control mice
|
|
• mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks or intramuscular treatment 50 ug tamoxifen at 2 weeks exhibit rare follicular tumors on the trunk and paws
|
|
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen and 1 umol CTX at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks unlike control mice
|
|
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment with 100 ug tamoxifen and 1 umol CTX at 6 to 8 weeks unlike control mice
• in 10 of 10 mice subjected to intramuscular treatment 50 ug tamoxifen at 2 weeks unlike control mice
|
|
• however, granulocyte-macrophage lineage specification is normal following treatment with tamoxifen
• following treatment with tamoxifen, the Lin-c-kithighSca-1high population is increased while the population of Lin-c-kitlowSca-1low are underrepresented compared to in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the thymus has lost its regular morphology and the cortex is no longer distinguishable from the medulla
|
|
• 15 days after the first injection of tamoxifen, thymus cellularity is decreased by 13-fold
|
|
• 19 days after the first injection of tamoxifen, the DN1 population is overrepresented while the DN2 and DN3 populations are underrepresented
• however, the DN4 population is stable after tamoxifen treatment
|
|
• 19 days after the first injection of tamoxifen, the relative number of immature double positive cells is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, the number of neutrophilic granulocytes is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, circulating B220high, IgD+ B cells are increased compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, mature B cells are overrepresented in the spleen compared to in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the relative number of mature single positive cells is increased compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, total lymphocyte fraction in the bone marrow is only slightly decreased compared to in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the number of double positive cells is almost depleted compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, the number of B220+ B cells in the spleen is reduced (4.71+/-2.33% compared to 13.98+/-3.74% in Ptch1tm1Jwnd control mice)
|
|
• following treatment with tamoxifen, CD43+ B cells are almost completely absent and fraction I and II immature B cells are decreased in the bone marrow compared to in Ptch1tm1Jwnd control mice
|
|
• at day15 through 19 after the first injection of tamoxifen, the number of T1 transitional B cells is reduced in the spleen compared to in Ptch1tm1Jwnd control mice
|
|
• following treatment with tamoxifen, bone marrow B220low pre-B cells are lower than in Ptch1tm1Jwnd control mice
|
|
• 19 days after the first injection of tamoxifen, the thymus has lost its regular morphology and the cortex is no longer distinguishable from the medulla
|
|
• 15 days after the first injection of tamoxifen, thymus cellularity is decreased by 13-fold
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival in mice subjected to intraperitoneal treatment with 5 mg tamoxifen at 8 weeks is 376 days compared with 441 days for control mice
|
|
• hamartomatous gastrointestinal cystic tumors in 4 of 32 mice subjected to intraperitoneal treatment with 5 mg tamoxifen at 8 weeks unlike control mice
|
|
• in 1 of 32 mice subjected to intraperitoneal treatment with 5 mg tamoxifen at 8 weeks unlike control mice
|
|
• epidermal cysts in 1 of 32 mice subjected to intraperitoneal treatment with 5 mg tamoxifen at 8 weeks unlike control mice
|
|
• epidermal cysts in 1 of 32 mice subjected to intraperitoneal treatment with 5 mg tamoxifen at 8 weeks unlike control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) between 11 and 25 weeks of age following doxycycline treatment at 3 weeks of age
• tumors exhibit features of human PDAC, including glandular tumor structures, exuberant stroma, local invasion into surrounding structures such as the duodenum, and distant metastases to the liver and lung
• mice show rapid tumor regression staring 48 hours and peaking at 72 hours following doxycycline withdrawal, with a reduction in tumor mass of about 50% after 1 week of doxycycline withdrawal; tumor regression is accompanied by decreased tumor cell proliferation and increased apoptosis
• withdrawal of doxycycline results in decreased glucose uptake and lactate production by cells in vitro
|
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) between 11 and 25 weeks of age following doxycycline treatment at 3 weeks of age
• tumors exhibit features of human PDAC, including glandular tumor structures, exuberant stroma, local invasion into surrounding structures such as the duodenum, and distant metastases to the liver and lung
• mice show rapid tumor regression staring 48 hours and peaking at 72 hours following doxycycline withdrawal, with a reduction in tumor mass of about 50% after 1 week of doxycycline withdrawal; tumor regression is accompanied by decreased tumor cell proliferation and increased apoptosis
• withdrawal of doxycycline results in decreased glucose uptake and lactate production by cells in vitro
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:186194 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal weight gain at 10 weeks of age
|
|
• slight increase in IFN-gamma levels
|
|
• slight increase in IL-6 levels
|
|
• slight increase in TNF levels
|
| N |
• mice show no joint inflammation at 10 weeks of age, cytokine levels (such as IL-1 alpha, IL-1 beta, and MCP-1) are severely reduced, and the autoinflammatory disease seen in Gt(ROSA)26Sortm1(OVAL/fla-GFP)Vnce and Lyz2tm1(cre)Ifo expressing mice is almost entirely ameliorated
|
|
• slight increase in IFN-gamma levels
|
|
• slight increase in IL-6 levels
|
|
• slight increase in TNF levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment at E6.5, all mice die at E10.5 due to failure of chorioallantoic fusion
|
|
• following tamoxifen treatment at E7.5, 50% of mice die at E10.5 due to failure of chorioallantoic fusion
|
| N |
• despite defects in hindlimb formation following treatment with tamoxifen at E9.5 and E10.5, mice exhibit normal hindlimb identity and forelimb development
• mice treated with tamoxifen at E11.5 exhibit normal hindlimb morphology
|
|
• following tamoxifen treatment at E7.5, limb buds form but are degenerating by E11.5 with hindlimb limited outgrowth
|
|
• following tamoxifen treatment at E9.5, the autopod of the hindlimb is thin
• following tamoxifen treatment at E9.5, the space between expression domains of Tbx2 and Tbx3 expression are narrower than in wild type mice and the hindlimb autopod contains fewer cells than in wild-type mice
• however, there is no reduction in cell proliferation rates in the hindlimb autopods of tamoxifen treated mice
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit abnormal anterior digits of the hindlimb
• following tamoxifen treatment at E10.5, some mice exhibit thin hindlimb digits I and II
|
|
• following tamoxifen treatment at E9.5, 33% of mice exhibit fusion of the anterior hindlimb digit; some with parital fusions of digits I and II and others with 4 digits indicating the loss of digit II or fusion of digits I and II
• following tamoxifen treatment at E10.5, 42% of mice exhibit fusion of the anterior hindlimb digits
|
|
• following tamoxifen treatment at E9.5, 67% of mice exhibit four symmetrical hindlimb digits
• following tamoxifen treatment at E9.5, digits I and II are partially fused in some mice while others have 4 digits indicating the loss of digit II or fusion of digits I and II
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit aplastic or severely hypoplastic femurs that do not articulate with the pelvis
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit aplastic or severely hypoplastic femurs that do not articulate with the pelvis
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit hypoplastic fibulas
|
|
• following tamoxifen treatment at E9.5 and E10.5, the hindlimb is shorter than in wild type mice at E14.5
|
|
• following tamoxifen treatment at E10.5, some mice exhibit a metatarsal of the first digit that originates near the middle of the metatarsal of digit two instead of near the tarsal bone
|
|
• following tamoxifen treatment at E7.5, limb buds form but are degenerating by E11.5 with hindlimb limited outgrowth
|
|
• following tamoxifen treatment at E6.5, mice die at E10.5 due to failure of chorioallantoic fusion
• following tamoxifen treatment at E7.5, 50% of mice die at E10.5 due to failure of chorioallantoic fusion
|
|
• following tamoxifen treatment at E9.5, 33% of mice exhibit fusion of the anterior hindlimb digit; some with parital fusions of digits I and II and others with 4 digits indicating the loss of digit II or fusion of digits I and II
• following tamoxifen treatment at E10.5, 42% of mice exhibit fusion of the anterior hindlimb digits
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit aplastic or severely hypoplastic femurs that do not articulate with the pelvis
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit aplastic or severely hypoplastic femurs that do not articulate with the pelvis
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit hypoplastic fibulas
|
|
• following tamoxifen treatment at E10.5, some mice exhibit a metatarsal of the first digit that originates near the middle of the metatarsal of digit two instead of near the tarsal bone
|
|
• following tamoxifen treatment at E9.5 or E10.5, mice exhibit abnormal pelvic connections and hypoplastic pelvises
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• restoration of normal thymus if cre induction with tamoxiphen occurs before 4 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E15.5 following tamoxifen treatment at E10.5
|
|
• at E15.5 following tamoxifen treatment at E10.5
|
|
• at E15.5 following tamoxifen treatment at E10.5
|
|
• at E15.5 following tamoxifen treatment at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hepatocytes from tamoxifen-treated mice are capable of activating OT-I CD8+ T cells unlike cells from un-induced mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit rescued total bone marrow and LSK cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Severe hypocellularity in Nle1tm1Cba/Nle1tm1.1Cota Gt(ROSA)26Sortm2(cre/ERT2)Brn/Gt(ROSA)26Sor+ bone marrow, with capillaries saturated with erythrocytes
|
• mice die 10 to 13 days after tamoxifen treatment
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• defects in secondary lymphoid organs in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• 7 to 9 days after tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit impaired biogenesis of large ribosomal subunit in hematopoietic stem cell and multipotent progenitor compared with control mice
|
| N |
• hematopoietic stem cell mobilization occurs normally in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit cell autonomous defects in hematopoiesis
|
|
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit impaired biogenesis of large ribosomal subunit in hematopoietic stem cell and multipotent progenitor compared with control mice
|
|
• in tamoxifen-treated mice
|
|
• severe in tamoxifen-treated mice
|
|
• decreased in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• reduced hematopoietic stem cell and multipotent progenitor quiescence in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• occasionally
|
|
• most tumors resemble diffuse large B cell lymphomas (in 6 of 9 mice)
|
|
• in 3 of 9 mice
|
|
• occasionally
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice exhibit increased serum alanine transaminase levels compared with un-induced mice
• however, un-induced mice exhibit normal alanine transaminase levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• occasionally
|
|
• most tumors resemble diffuse large B cell lymphomas (in 6 of 9 mice)
|
|
• in 3 of 9 mice
|
|
• occasionally
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated embryonic stem cells exhibit normal viability and self-renewal
|
|
• tamoxifen-treated embryonic stem cells fail to differentiate in vitro and in vivo
|
|
• tamoxifen-treated embryonic stem cells and embryonic fibroblasts exhibit defective telomere maintenance
|
|
• tamoxifen-treated embryonic stem cells exhibit nonsense-mediated mRNA decay
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the lungs of mice infected with N. brasiliensis
|
|
• mice exhibit reduced helminthes Nippostrongylus brasiliensis expulsion compared with control mice
|
|
• in the lungs of mice infected with N. brasiliensis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the lungs of mice infected with N. brasiliensis
|
|
• slightly less in an anti-NP response
|
|
• in lung CD4+ T cells of mice infected with N. brasiliensis
|
|
• in lung CD4+ T cells of mice infected with N. brasiliensis
|
|
• mice fail to expel the helminth Nippostrongylus brasiliensis
|
|
• in the lungs of mice infected with N. brasiliensis
|
|
• slightly less in an anti-NP response
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as severe as in mice wild-type for Cd9
|
|
• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
|
|
• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
• compared to in mice homozygous for a conditional allele
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die by 30 weeks of age
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tamoxifen-treated mice exhibit enrichment in phospholipid total n-3 polyunsaturated fatty acid (predominantly docosahexaenoic acid) with lesser contributions to total relative n-3 polyunsaturated fatty acid enrichment from 22:5n-3 in the liver, kidney and muscle compared with control mice
• tamoxifen-treated mice exhibit a reduction in n-6 polyunsaturated fatty acid species, 22:5n-6 and 22:4n-6 in the liver, kidney and a small overall decrease in total n-6 polyunsaturated fatty acid content in the kidney and liver compared with control mice
• tamoxifen treated mice exhibit a small difference in n-6/n-3 polyunsaturated fatty acid ratio compared with control mice
• however, mice exhibit normal total saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tamoxifen-treated mice exhibit enrichment in phospholipid total n-3 polyunsaturated fatty acid (predominantly docosahexaenoic acid) with lesser contributions to total relative n-3 polyunsaturated fatty acid enrichment from 22:5n-3 in the liver, kidney and muscle compared with control mice
• tamoxifen-treated mice exhibit a reduction in n-6 polyunsaturated fatty acid species, 22:5n-6 and 22:4n-6 in the liver, kidney and a small overall decrease in total n-6 polyunsaturated fatty acid content in the kidney and liver compared with control mice
• tamoxifen treated mice exhibit a small difference in n-6/n-3 polyunsaturated fatty acid ratio compared with control mice
• however, mice exhibit normal total saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation
|
|
• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit a 2-fold reduction in S-phase cells and an increase in G1 phase cell compared with control cells
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit growth arrest compared with control cells
|
|
• in tamoxifen-treated mouse embryonic fibroblasts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• sham-irradiated, tamoxifen-treated mice show no significant differences in spontaneous tumor development or survival relative to mice that are heterozygous for Trp53tm1Brn and Gt(ROSA)26Sortm1(cre/ERT2)Tyj but wild-type for Setd4
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
• gamma-irradiated tamoxifen-treated mice die mainly of non-disseminated thymic lymphomas, unlike mice that are homozygous for Setd4tm1c(KOMP)Wtsiand heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj where tumors are widely disseminated to other organs
|
|
• in gamma-irradiated tamoxifen-treated mice, thymic lymphomas are significantly larger in size/weight relative to those in mice that are only homozygous for Setd4tm1c(KOMP)Wtsiand heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas
|
|
• sham-irradiated, tamoxifen-treated double mutant mice show accelerated spontaneous tumor development relative to mice that are only homozygous for Trp53tm1Brn and heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• expanded crypts in the ileum of doxycycline-treated mice
|
|
• increased cell proliferation in the intestine of doxycycline-treated mice without an increase in Lgr5+ cells
|
|
• in the intestine of doxycycline-treated mice without an increase in Lgr5+ cells
|
|
• expanded crypts in the ileum of doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lyzsozyme+ Paneth cells in doxycycline-treated mice are not restricted to the base of the crypt unlike in control cells
|
|
• expanded crypts in the ileum of doxycycline-treated mice
|
|
• increased cell proliferation in the intestine of doxycycline-treated mice with an increase in intestinal stem Lgr5+ cells
• increased proliferation of intestinal stem cells in the intestine of doxycycline-treated mice
• expansion of intestinal stem cells is cell autonomous in doxycycline treated mice
|
|
• in the intestine of doxycycline-treated mice with an increase in Lgr5+ intestinal stem cells
• increased proliferation of intestinal stem cells in the intestine of doxycycline-treated mice
• expansion of intestinal stem cells is cell autonomous in doxycycline treated mice
|
|
• lyzsozyme+ Paneth cells in doxycycline-treated mice are not restricted to the base of the crypt unlike in control cells
|
|
• expanded crypts in the ileum of doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• both sexes of tamoxifen-treated mice fed a Western diet for 12 weeks show a significant decrease in atherosclerotic lesion size in whole aortas as well as smaller lesion areas and less lipid deposition in the aortic sinuses than control mice
• ACTA2 staining of aortic sinuses showed a significant reduction in the vascular smooth muscle cell (VSMC) content of atherosclerotic lesions in both sexes
|
| N |
• both male and female mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show no significant differences in plasma glucose levels relative to controls
|
|
|
• male, but not female, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show a modest reduction in plasma cholesterol levels relative to controls
|
|
|
• female, but not male, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks exhibit a significant increase in plasma triglyceride levels relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• observed in about 58% of viable embryos collected at 14.5 days post coitus
• folate injections performed on pregnant females does not affect penetrance
|
|
• observed in about 58% of viable embryos collected at 14.5 days post coitus
• folate injections performed on pregnant females does not affect penetrance
|
|
• observed with around 83% frequency in viable embryos collected at 14.5 days post coitus
• folate injections performed on pregnant females does not affect penetrance
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die around E15.5
|
|
• palatal shelves are smaller
|
|
• at E15.5 almost all soft palates are fusing with the degenerating epithelial beam at the tensor veli palatini muscle level
|
|
• absence of levator veli palatini, tensor veli palatini, and palatopharyngeus muscles
|
|
• absence of levator veli palatini muscle
|
|
• absence of palatopharyngeus muscle
|
|
• absence of tensor veli palatini muscle
|
|
• absence of levator veli palatini, tensor veli palatini, and palatopharyngeus muscles
|
|
• absence of levator veli palatini muscle
|
|
• absence of palatopharyngeus muscle
|
|
• absence of tensor veli palatini muscle
|
|
• absence of superior pharyngeal constrictor muscle
|
|
• palatal shelves are smaller
|
|
• at E15.5 almost all soft palates are fusing with the degenerating epithelial beam at the tensor veli palatini muscle level
|
|
• absence of levator veli palatini, tensor veli palatini, and palatopharyngeus muscles
|
|
• absence of levator veli palatini muscle
|
|
• absence of palatopharyngeus muscle
|
|
• absence of tensor veli palatini muscle
|
|
• palatal shelves are smaller
|
|
• at E15.5 almost all soft palates are fusing with the degenerating epithelial beam at the tensor veli palatini muscle level
|
|
• absence of levator veli palatini, tensor veli palatini, and palatopharyngeus muscles
|
|
• absence of levator veli palatini muscle
|
|
• absence of palatopharyngeus muscle
|
|
• absence of tensor veli palatini muscle
|
|
• absence of superior pharyngeal constrictor muscle
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• moribund as early as 3 days post tamoxifen treatment
• 75% of mice die 9 days after tamoxifen treatment
• mice treated with a low dose of tamoxifen exhibit increased death associated with tumorigenesis
|
|
• tamoxifen-treated mice exhibit increased cell proliferation in the intestinal epithelium compared with control mice
|
|
• loss of architecture in tamoxifen-treated mice with reduction in numbers of differentiated cells, cells showing dysplastic nuclear atypia, widespread crypt elongation, increased crypt fission and reduction in villous length
|
|
• in tamoxifen-treated mice
|
|
• reduced numbers in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit a decrease of Alcian Blue positive goblet cells compared with control mice
|
|
• elongated in tamoxifen-treated mice
|
|
• altered distribution in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in 6 of 16 tamoxifen-treated mice, 2 of which are adenomas with high-grade dysplasia and 2 are invasive adenocarcinoma
• 5 of 6 tumors are located in the caecum
|
|
• tamoxifen-treated mice exhibit increased incidence of tumorigenesis, including lymphomas/leukemias and solid tumors (angiosarcoma, gastrointestinal adenoma, gastrointestinal adenocarcinoma and lung carcinoma)
|
|
• in 6 of 16 tamoxifen-treated mice, 2 of which are adenomas with high-grade dysplasia and 2 are invasive adenocarcinoma
• 5 of 6 tumors are located in the caecum
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit zone 3 hydropic changes indicative of malnutrition unlike control mice
|
|
• in tamoxifen-treated mice
|
|
• reduced numbers in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit a decrease of Alcian Blue positive goblet cells compared with control mice
|
|
• tamoxifen-treated mice exhibit increased cell proliferation in the intestinal epithelium compared with control mice
|
|
• elongated in tamoxifen-treated mice
|
|
• altered distribution in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no differences in the morphological polarization, motility, or chemotactic efficiency of macrophages are seen in a complement C5a gradient chemotaxis assay
• macrophages exhibit normal Golgi morphology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired intestinal epithelial renewal in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced cycling and proliferation of intestinal stem cells
• however, proliferation rates are normal
|
|
• reduced cycling and proliferation of intestinal stem cells
• however, proliferation rates are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased CD8+ effector T cells in the peripheral blood lymphocytes compared with control mice and more so than in Tcf7tm1Cle homozygotes following infection with actA- L. monocytogenes-expressing ovalbumin
• decreased memory precursors and memory CD8+ T cells compared with control mice and more so than in Tcf7tm1Cle homozygotes following infection with actA- L. monocytogenes-expressing ovalbumin
|
|
• following infection with actA- L. monocytogenes-expressing ovalbumin, memory CD8+ T cells exhibit impaired maturation, function and recall response compared with control mice
|
|
• from CD8+ effector T cells following infection with actA- L. monocytogenes-expressing ovalbumin
|
|
• decreased CD8+ effector T cells in the peripheral blood lymphocytes compared with control mice and more so than in Tcf7tm1Cle homozygotes following infection with actA- L. monocytogenes-expressing ovalbumin
• decreased memory precursors and memory CD8+ T cells compared with control mice and more so than in Tcf7tm1Cle homozygotes following infection with actA- L. monocytogenes-expressing ovalbumin
|
|
• following infection with actA- L. monocytogenes-expressing ovalbumin, memory CD8+ T cells exhibit impaired maturation, function and recall response compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit rescue of growth retardation and osteosclerotic phenotypes seen in single Gt(ROSA)26Sortm1(Notch1)Dam conditional mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• moribund as early as 3 days post tamoxifen treatment
• 75% of mice die 9 days after tamoxifen treatment
• mice treated with a low dose of tamoxifen exhibit increased death associated with tumorigenesis
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit increased cell proliferation in the intestinal epithelium compared with control mice
|
|
• loss of architecture in tamoxifen-treated mice with reduction in numbers of differentiated cells, cells showing dysplastic nuclear atypia, widespread crypt elongation, increased crypt fission and reduction in villous length
|
|
• in tamoxifen-treated mice
|
|
• reduced numbers in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit a decrease of Alcian Blue positive goblet cells compared with control mice
|
|
• elongated in tamoxifen-treated mice
|
|
• altered distribution in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in 6 of 16 tamoxifen-treated mice, 2 of which are adenomas with high-grade dysplasia and 2 are invasive adenocarcinoma
• 5 of 6 tumors are located in the caecum
|
|
• tamoxifen-treated mice exhibit increased incidence of tumorigenesis, including lymphomas/leukemias and solid tumors (angiosarcoma, gastrointestinal adenoma, gastrointestinal adenocarcinoma and lung carcinoma)
|
|
• in 6 of 16 tamoxifen-treated mice, 2 of which are adenomas with high-grade dysplasia and 2 are invasive adenocarcinoma
• 5 of 6 tumors are located in the caecum
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit zone 3 hydropic changes indicative of malnutrition unlike control mice
|
|
• in tamoxifen-treated mice
|
|
• reduced numbers in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit a decrease of Alcian Blue positive goblet cells compared with control mice
|
|
• tamoxifen-treated mice exhibit increased cell proliferation in the intestinal epithelium compared with control mice
|
|
• elongated in tamoxifen-treated mice
|
|
• altered distribution in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no increase in heart weight, no dilation, and no fibrosis when tamoxifen is used to induce loss of expression in neonatal mice unlike when expression is absent in embryonic stages
|
|
• in cultured cardiomyocytes after tamoxifen induction 22% become binucleated while very few cells were binucleate before tamoxifen exposure
|
|
• increase in the proportion of cardiomyocytes with unresolved cytokinetic midbody structures indicating failed abscission
|
|
• increase in the proportion of cardiomyocytes with unresolved cytokinetic midbody structures indicating failed abscission
|
|
• increase in the proportion of cardiomyocytes with unresolved cytokinetic midbody structures indicating failed abscission
|
|
• increase in the proportion of cardiomyocytes with unresolved cytokinetic midbody structures indicating failed abscission
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cultured tamoxifen-treated DN1, DN2, and DN3 thymocytes differentiate into natural killer-like cells and kill stromal feeder cells unlike similarly treated wild-type thymocytes
• cultured spleen and thymus cells treated with tamoxifen exhibit differentiation into induced T to natural killer cells (ITNK) unlike cells from similarly treated wild-type cells
• tamoxifen-treated thymocytes transplanted into Rag2 Il2rg null mice exhibit an increase in ITNK cells compared with mice transplanted with similarly treated wild-type mice
|
|
• reprogrammed induced T to natural killer cells (ITNK) transplanted into Rag2 Il2rg null suppress metastasis of transplanted B16F10 melanoma cells
|
|
• cultured tamoxifen-treated DN1, DN2, and DN3 thymocytes differentiate into natural killer-like cells and kill stromal feeder cells unlike similarly treated wild-type thymocytes
• cultured spleen and thymus cells treated with tamoxifen exhibit differentiation into induced T to natural killer cells (ITNK) unlike cells from similarly treated wild-type cells
• tamoxifen-treated thymocytes transplanted into Rag2 Il2rg null mice exhibit an increase in ITNK cells compared with mice transplanted with similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die early with lymphoma/thymoma
|
|
• some mice have small mammary tumors
|
|
• some mice have small mammary tumors
|
|
• some mice have small mammary tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is reduced compared to mutant mice wild-type for Trp53
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
|
• at a lower rate than in mutant mice homozygous for Trp53tm1Brn
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:170898 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced adult dorsal root ganglia regeneration following sciatic nerve crush injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tamoxifen treatment provokes infertility in females regardless of genotype
• after treatment is discontinued, control animals fully recover fertility, whereas mutant females remain infertile
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• almost complete ablation of germinal centers in response to T cell dependent immunization
• the few remaining germinal center B cells have escaped cre mediated recombination
|
|
• almost complete ablation of germinal centers in response to T cell dependent immunization
• the few remaining germinal center B cells have escaped cre mediated recombination
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• enforced expression of human MYC rescues germinal center formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are viable
|
| N |
• female mice exhibit normal onset of puberty, ovalutory cyclicity, and fertile
|
|
|
• at P20
|
|
|
• female mice exhibit slightly prolonged phases of cornification compared with wild-type mice
|
|
• slightly increased in female mice between P31 and P46
|
|
|
• at P20
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
|
• B cell development in the spleen is altered
• however, mice exhibit normal B cell development in the bone marrow
|
|
• in the spleen
|
|
• in the spleen
|
|
• in re-circulating B cells
• slightly in the spleen
|
|
• in the peritoneal cavity
|
|
• in the peritoneal cavity
|
|
• 5 times
|
|
• doubled in the spleen
|
|
• diminished in size
|
|
• after NP-CGG stimulation with diminished NP-specific IgM and IgG1
|
|
• enlarged in size
|
|
• 7 times
|
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
|
• after NP-Ficoll stimulation
|
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
|
• enlarged in response to anti-CD40 antibodies and IL4
|
|
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
|
• B cell development in the spleen is altered
• however, mice exhibit normal B cell development in the bone marrow
|
|
• in the spleen
|
|
• in the spleen
|
|
• in re-circulating B cells
• slightly in the spleen
|
|
• in the peritoneal cavity
|
|
• in the peritoneal cavity
|
|
• 5 times
|
|
• doubled in the spleen
|
|
• diminished in size
|
|
• after NP-CGG stimulation with diminished NP-specific IgM and IgG1
|
|
• enlarged in size
|
|
• 7 times
|
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
|
• after NP-Ficoll stimulation
|
|
• diminished NP-specific IgM and IgG1 after NP-CGG stimulation
|
|
• enlarged in response to anti-CD40 antibodies and IL4
|
|
• slightly in vivo
• in vitro without stimulation and after stimulation with anti-CD40 antibodies or LPS
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T1 B cells do not proceed to T2 B cell stage but directly develop into marginal zone B cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the bone marrow
|
|
• in the bone marrow
|
|
• enlarged
|
|
• T1 B cells do not proceed to T2 B cell stage but directly develop into marginal zone B cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the bone marrow
|
|
• in the bone marrow
|
|
• enlarged
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• starburst amacrine cells in flat mount retinas show excess and aberrant light-evoked inhibitory postsynaptic currents
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• frequent olfactory receptor switching at 6 weeks
|
|
• frequent olfactory receptor switching at 6 weeks
|
|
• frequent olfactory receptor switching at 6 weeks
|
|
• frequent olfactory receptor switching at 6 weeks
|
|
• frequent olfactory receptor switching at 6 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• retinal capillaries from tamoxifen-treated mice are more resistant to oxygen-induced vaso-obliteration compared with control capillaries
|
|
• tamoxifen-treated mice exhibit reduced capillary regression during normal developmental capillary remodeling compared with control mice
|
|
• retinal capillaries from tamoxifen-treated mice are more resistant to oxygen-induced vaso-obliteration compared with control capillaries
|
|
• tamoxifen-treated mice exhibit reduced capillary regression during normal developmental capillary remodeling compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mouse embryonic fibroblasts treated with tamoxifen and nocodazole exhibit reduced cell cycle arrest compared with similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adult mice die 7 days after tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit reduced cell proliferation with abnormal nuclei and mitotic increased nuclear area compared with wild-type mice
|
|
• tamoxifen-treated mice exhibit atrophy of the small intestine compared with wild-type mice
|
|
• 6 days after tamoxifen treatment, mice exhibit a greater than 80% loss of villus epithelium compared with wild-type mice
however, no increase in apoptosis is observed
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit supernumerary centrosomes compared with similarly treated wild-type cells
|
|
• tamoxifen-treated mouse embryonic fibroblasts stimulated with serum exhibit abnormal nuclei including binuclear, multi-lobed, and donut-shaped nuclei compared to similarly treated wild-type cells
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit a delayed entry into mitosis (G2 delay) compared with similarly treated wild-type mice
• tamoxifen-treated mouse embryonic fibroblasts exhibit mitotic errors including chromatin bridges, failed nuclear segregation, cytokinesis failure, chaotic multipolar spindles, and supernumerary centrosomes compared with similarly treated wild-type cells
|
|
• following tamoxifen treatment, mouse embryonic fibroblasts exhibit severely impaired proliferation compared with similarly treated wild-type cells
|
|
• tamoxifen-treated mice exhibit reduced cell proliferation with abnormal nuclei and mitotic increased nuclear area compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following filament middle cerebral artery occlusion, mice exhibit reduced infarct volume compared with similarly treated Notch3Gt(PST033)Byg homozygotes
|
|
• following filament middle cerebral artery occlusion, mice exhibit reduced infarct volume compared with similarly treated Notch3Gt(PST033)Byg homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• female mice exhibit normal onset of puberty, ovalutory cyclicity, and fertile
|
|
|
• female mice exhibit slightly prolonged phases of cornification compared with wild-type mice
|
|
• the number of gonadotrophin-releasing hormone neurons in the hypothalamus of female mice is decreased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the cleft lip phenotype observed in Pbx1tm1.1Koss/Pbx1tm1.1Koss Pbx2tm1Mlc/Pbx2+ Tg(Tcfap2a*-cre)1Will is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) at a median age of 7.9 weeks following doxycycline treatment at 3 weeks of age
|
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) at a median age of 7.9 weeks following doxycycline treatment at 3 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:186194 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• clara cell numbers recover after tamoxifen and/or naphthalene lung injury regardless of presence or absence of pulmonary neuroendocrine cells
|
|
• pulmonary neuroendocrine cells ablated by tamoxifen treatment are not replaced at 1, 6, 10, and 12 months after treatment
• naphthalene lung injury fails to induce restoration of this cell type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen stimulation
• however, apoptosis is rescued by IL7 treatment
|
|
• T lymphocytes exhibit increased mitochondria and endoplasmic reticulum content compared with wild-type cells
|
|
• following tamoxifen stimulation
• however, apoptosis is rescued by IL7 treatment
|
|
• T lymphocytes exhibit increased mitochondria and endoplasmic reticulum content compared with wild-type cells
|
|
• following tamoxifen stimulation
• however, apoptosis is rescued by IL7 treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• telencepepahlic vesicle development is often asymmetric in embryos, with the right side being more severely affected
• very small telencephalic vesicle is sometimes observed at the 8-10 somite stage
|
|
• development of optic vesicles is often asymmetric with right side more severely affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit a dramatic reduction of S phase entry compared with control mice
|
|
• tamoxifen-treated primary keratinocyte cultures exhibit increased expression of differentiation markers compared with control cells
|
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased proliferation and a 2- to 6-fold increase in slow cycling cells in passage 4 and 5 compared with control mice
|
|
• in tamoxifen-treated mouse embryonic fibroblasts
|
|
• tamoxifen-treated primary keratinocyte cultures exhibit increased expression of differentiation markers compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cheek injection of capsaicin does not evoke pain behavior (forepaw facial wiping), in contrast to robust facial wiping observed in treated wild-type
|
|
• mice have impaired nociceptive responses, showing increased latencies in tail-immersion and hot plate paradigms
|
|
• robust itch behavior is observed after cheek injection of capsaicin compared to little hindpaw scratching seen in treated wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit impaired somatostatin+ cortical interneuron differentiation compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• splenomegaly in all terminally ill mice
|
|
• plasma cell formation is severely impeded 10 days after primary and secondary immunization
|
|
• mice show increased numbers of germinal center B cells at day 10 after primary immunizations
|
|
• small, but significant, increase of the fraction of germinal center B cells in the S and G2 phases of the cell cycle
|
|
• reduction in total as well as sheep red blood cell-specific IgG1, but not IgM, antibodies 10 days after primary and secondary immunization
|
|
• splenomegaly in all terminally ill mice
|
|
• plasma cell formation is severely impeded 10 days after primary and secondary immunization
|
|
• mice show increased numbers of germinal center B cells at day 10 after primary immunizations
|
|
• small, but significant, increase of the fraction of germinal center B cells in the S and G2 phases of the cell cycle
|
|
• reduction in total as well as sheep red blood cell-specific IgG1, but not IgM, antibodies 10 days after primary and secondary immunization
|
|
• occasional lymphadenopathy
|
|
• hepatomegaly in one mouse
|
|
• shortened survival
|
|
• shortened survival
|
|
• spleens and lymph nodes show presence of large cells with a diffuse growth pattern, resembling diffuse large B cell lymphoma (DLBCL)
• lymphoproliferations are of clonal origin
• 5 of 6 DLBCLs are consistent with activated B cell-DLBCL
|
|
• hepatomegaly in one mouse
|
|
• splenomegaly in all terminally ill mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal B cell development in the bone marrow and spleen
|
|
• following with activation LPS, less so when activated with LPS plus IL4
|
|
• following activated with LPS and IL4, mice exhibit decreased IgG1+ cells, indicating reduced class switch recombination, compared with wild-type mice
|
|
• following immunization with NP-CGG in alum, splenic B cells exhibit reduced mutation frequency in the rearranged Vh186.2 H chains compared with wild-type cells
• Peyer's patch B cells exhibit reduced accumulation of mutation at the intron downstream of rearranged V genes compared with wild-type cells
|
|
• following with activation LPS, less so when activated with LPS plus IL4
|
|
• following activated with LPS and IL4, mice exhibit decreased IgG1+ cells, indicating reduced class switch recombination, compared with wild-type mice
|
|
• following immunization with NP-CGG in alum, splenic B cells exhibit reduced mutation frequency in the rearranged Vh186.2 H chains compared with wild-type cells
• Peyer's patch B cells exhibit reduced accumulation of mutation at the intron downstream of rearranged V genes compared with wild-type cells
|
|
• following with activation LPS, less so when activated with LPS plus IL4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Shortened villi in the small intestine of Cdc25atm1Hpw/Cdc25atm1.1Hpw Cdc25btm1Pjd/Cdc25btm1Pjd Cdc25ctm1Hpw/Cdc25ctm1Hpw Gt(ROSA)26Sortm1(cre/ERT)Brn/Gt(ROSA)26Sor+ (TKO) mice
|
• adult mice die within 1 week of initial 4-hydroxytamoxifen (OHT) injection
|
|
• adult mice exhibit significant weight loss (20%) within 1 week of initial tamoxifen injection
|
|
• profound cell atrophy in the crypts is observed in OHT-treated mice; crypts are >40% smaller in mutants than Cdc25a-single knockout controls, with the crypt width being decreased more significantly than the depth
• a 70% loss of epithelial cells per crypt is detected, but no difference in mature Paneth cells is observed
• decreased proliferation of epithelial cells is observed, with no significant increase in apoptotic cell numbers; this results in premature differentiation of cell progenitors below Paneth cell compartments in crypts
• crypts have increased numbers of cells exhibiting early differentiation with no crypt base columnar (CBC) cells
|
|
• villi are lined with shorter, less-dense enterocytes in proximal regions; complete loss of distal villi is observed in some areas
|
|
• significant loss of villus height in proximal and distal regions is observed in mutants after OHT treatment
|
|
• 6 days following the final of 3 consecutive injections of tamoxifen, length of small intestine is shortened by 40% compared to controls
|
|
• profound cell atrophy in the crypts is observed in OHT-treated mice; crypts are >40% smaller in mutants than Cdc25a-single knockout controls, with the crypt width being decreased more significantly than the depth
• a 70% loss of epithelial cells per crypt is detected, but no difference in mature Paneth cells is observed
• decreased proliferation of epithelial cells is observed, with no significant increase in apoptotic cell numbers; this results in premature differentiation of cell progenitors below Paneth cell compartments in crypts
• crypts have increased numbers of cells exhibiting early differentiation with no crypt base columnar (CBC) cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no difference in villi height is after 4-hydroxytamoxifen treatment observed after in contrast to triple knockout mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• intestinal crypt stem cells show increased cell death following tamoxifen administration
|
|
• 3 weeks after tamoxifen administration, mutant villus epithelial cells show disrupted cell polarity, as indicated by disorganized nuclear alignment
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration
|
|
• 3 weeks after tamoxifen administration, more mutant stem cells in intestinal crypts undergo mitosis compared to control stem cells
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration, indicating reduced clonal expansion of mutant stem cells
|
|
• 2 weeks after tamoxifen administration, mutant stem cells in intestinal crypts fail to give rise to Paneth cells
|
|
• 3 weeks after tamoxifen administration, mutant villus epithelial cells show disrupted cell polarity, as indicated by disorganized nuclear alignment
|
|
• 3 weeks after tamoxifen administration, more mutant stem cells in intestinal crypts undergo mitosis compared to control stem cells
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration, indicating reduced clonal expansion of mutant stem cells
|
|
• 2 weeks after tamoxifen administration, mutant stem cells in intestinal crypts fail to give rise to Paneth cells
|
|
• intestinal crypt stem cells show increased cell death following tamoxifen administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by P20
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 31 days compared with mice with wild-type Hk2 that die by P20
|
|
• increased micro-vascularization
|
|
• compared to in mice with wild-type Hk2
|
|
• all mice develop tumors with reduced growth and at increased latency compared to in mice with wild-type Hk2
|
|
• all mice develop tumors with increased latency compared to in mice with wild-type Hk2
|
|
• reduced cerebellar granule neuron progenitors proliferation
|
|
• all mice develop tumors with reduced growth and at increased latency compared to in mice with wild-type Hk2
|
|
• reduced cerebellar granule neuron progenitors proliferation
|
|
• increased micro-vascularization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mural cell (pericytes and vascular smooth muscle cells) densities are lower than in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased blood-brain barrier (BBB) permeability compared with wild-type mice
• however, imatinib-treatment reverses increased BBB permeability without improving blood vessel morphology
|
|
• astrocyte end-feet are mis-localized compared to in wild-type mice
|
|
• capillary diameter is increased compared to in wild-type mice
|
|
• capillary density is reduced compared to in wild-type mice
|
|
• pericyte coverage is less than in wild-type mice but not as severely as in Pdgfbtm3.1Cbet homozygotes
|
|
• mice exhibit increased blood-brain barrier (BBB) permeability compared with wild-type mice
• however, imatinib-treatment reverses increased BBB permeability without improving blood vessel morphology
|
|
• astrocyte end-feet are mis-localized compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• viable double mutant embryos are recovered in significantly reduced numbers at E14.5 and E17.5 compared to cre-negative/R26DTA embryos
|
|
• the few animals surviving past birth are smaller than littermates
|
| N |
• ACTH hormone levels are not significantly altered in mutants at E14.5
• at E17.5 and P0, numbers of ACTH, TPIT, PIT-1 (ie. thyrotropes, somatotropes, and lactotropes), PRL, and GH-positive cells in the anterior pituitary are not significantly reduced compared to controls
|
|
• at E14.5, cells positive for alphaGSU expression (ie. gonadotrophs) are reduced in the caudomedial portion of the anterior pituitary
• GATA2-positive cells are absent from the caudomedial region of the pituitary but are still present in the rostral tip
|
|
• at E14.5, cells positive for alphaGSU expression (ie. gonadotropes) are reduced in the caudomedial portion of the anterior pituitary
• in animals at P0, LH beta-positive gonadotrope cells are decreased by about 90% compared to controls; FSH beta-positive gonadotrope cells are decreased slightly also
• at P0, numbers of LH/SF1 or FSH/SF1 double positive cells are significantly decreased
• at P0, about 90% of bihormonal (LH beta/FSH beta positive) cells are missing compared to controls
|
|
• at E14.5, cells positive for alphaGSU expression (ie. gonadotrophs) are reduced in the caudomedial portion of the anterior pituitary
• GATA2-positive cells are absent from the caudomedial region of the pituitary but are still present in the rostral tip
|
|
• at E14.5, cells positive for alphaGSU expression (ie. gonadotropes) are reduced in the caudomedial portion of the anterior pituitary
• in animals at P0, LH beta-positive gonadotrope cells are decreased by about 90% compared to controls; FSH beta-positive gonadotrope cells are decreased slightly also
• at P0, numbers of LH/SF1 or FSH/SF1 double positive cells are significantly decreased
• at P0, about 90% of bihormonal (LH beta/FSH beta positive) cells are missing compared to controls
|
|
• numbers of Lhx-positive interneurons are decreased in the V2 interneuron region of the spinal cord at E14.5, but populations of motorneurons (ventral) are not affected
• at E14.5, V2a interneurons expressing LHX3 and CHX10 are reduced in number
|
|
|
• of 2 surviving male mutants, one was infertile
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neonatal lethality observed in Kdm6bGt(XB814)Byg homozygotes is rescued
|
| N |
• mice exhibit normal pre-Botzinger complex
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mice develop mono- and oligoclonal lymphomas
|
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
|
• 8 times more in the spleen
• 4-fold in lymph nodes
• increased percent of IgM+IgD+ B cells in the spleen and lymph nodes
• however, absolute numbers in the bone marrow are normal
|
|
• 3 times more in the spleen
|
|
• enlarged
|
|
• prolonged survival in vitro
|
|
• Ig class switch recombination is achieved in the presence of IL4 indicating constitutive CD40 signaling
|
|
• activated B cells in the spleen and lymph node
|
|
• spontaneous
|
|
• activated T cells with a shift toward activated and memory-type T cells
|
|
• in mice older than 12 months showing signs of disease
|
|
• following immunization with hapten conjugated to the carrier chicken gammaglobulin, mice exhibit reduced recruitment/maintenance of B cells within the germinal centers of the spleen compared with wild-type mice
|
|
• with extreme splenomegaly, enlarged inguinal lymph nodes, hepatomegaly and nodular infiltrates in the kidney, lung and liver in mice older than 12 months showing signs of disease
|
|
• in mice older than 12 months showing signs of disease
|
|
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
|
• 8 times more in the spleen
• 4-fold in lymph nodes
• increased percent of IgM+IgD+ B cells in the spleen and lymph nodes
• however, absolute numbers in the bone marrow are normal
|
|
• 3 times more in the spleen
|
|
• enlarged
|
|
• prolonged survival in vitro
|
|
• Ig class switch recombination is achieved in the presence of IL4 indicating constitutive CD40 signaling
|
|
• activated B cells in the spleen and lymph node
|
|
• spontaneous
|
|
• activated T cells with a shift toward activated and memory-type T cells
|
|
• in mice older than 12 months showing signs of disease
|
|
• at 8 weeks
• extreme in mice older than 12 months showing signs of disease
|
|
• 3.5-fold at 8 weeks
• 20- to 40-fold in mice older than 12 months showing signs of disease
|
|
• spontaneous
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in un-induced mice
• however, tamoxifen induction rescues thymus size
|
|
• Vgamma4+ gamma delta T cells in the peripheral lymph nodes, spleen, lung and liver despite tamoxifen treatment of adult mice
|
|
• absent IL17+ cells despite tamoxifen treatment of adult mice
|
|
• Vgamma1+ gamma delta T cells in the spleen, lung and liver despite tamoxifen treatment of adult mice
|
|
• in un-induced mice
• however, tamoxifen induction rescues thymus size
|
|
• Vgamma4+ gamma delta T cells in the peripheral lymph nodes, spleen, lung and liver despite tamoxifen treatment of adult mice
|
|
• absent IL17+ cells despite tamoxifen treatment of adult mice
|
|
• Vgamma1+ gamma delta T cells in the spleen, lung and liver despite tamoxifen treatment of adult mice
|
|
• in un-induced mice
• however, tamoxifen induction rescues thymus size
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• impaired in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit splenomegaly and become terminally ill unlike control mice
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• impaired in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• impaired in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit splenomegaly and become terminally ill unlike control mice
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
• in an in vitro tumor killing assay, CD4+ T cells exhibit reduced tumor killing compared with control cells
• however, CD4+ T cells exhibit normal prevention of tumor outgrowth in vivo and elimination of nontransformed L,p1+ B cells upon transfer
|
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
• in vivo, CD8+ T cells exhibit reduced prevention of tumor outgrowth compared with control cells
• however, CD8+ T cell exhibit normal tumor killing in vitro and elimination of nontransformed L,p1+ B cells upon transfer
|
|
• minor in T cells co-cultured with tumor or B cells
|
|
• minor in T cells co-cultured with tumor or B cells
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• impaired in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the spleen and bone marrow
• absent CD19+Fas+ B cells at 8 to 11 weeks in the spleen
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at 6 to 12 weeks in the bone marrow
|
|
• at P8, mice exhibit an increase in CD19+ B cells in the spleen compared with control mice
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• at P8, but not P3, in the spleen
• of activated T cells in the bone marrow at 6 to 12 weeks
|
|
• in an in vitro tumor killing assay, CD4+ T cells exhibit reduced tumor killing compared with control cells
• however, CD4+ T cells exhibit normal prevention of tumor outgrowth in vivo and elimination of nontransformed L,p1+ B cells upon transfer
|
|
• the CD8+ compartment of the bone marrow of mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit a 2-fold increase in cells expressing IFN-gamma, TNF-alpha, IL4 and IL17
• in vivo, CD8+ T cells exhibit reduced prevention of tumor outgrowth compared with control cells
• however, CD8+ T cell exhibit normal tumor killing in vitro and elimination of nontransformed L,p1+ B cells upon transfer
|
|
• 2 weeks after treatment with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1)
|
|
• after 2 weeks, mice treated with a cocktail of depleting antibodies (anti-CD4, anti-CD8 and anti-Thy1) exhibit rapid expansion of Lmp1+ B cell blasts largely confined to peripheral lymphoid organs and the bone marrow with some infiltration into the liver and rarely into lungs and kidneys compared with control mice
• however, mice treated with one depleting antibodies (anti-CD4, anti-CD8, anti-Thy1 or anti-CD4 and anti-CD8) do not exhibit expansion of B cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• body weights mice from 4 to 7 weeks after birth are significantly lower than those of wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show some reduction in the germinal center B cell fraction at day 10 after primary and secondary immunization
|
|
• hyperplasia of B cells in the spleen and bone marrow at 550-600 days
|
|
• hyperplasia of plasma cells in the spleen and bone marrow at 550-600 days
• clonal or oligoclonal plasma cell expansions
|
|
• large numbers of cells expressing intracellular Ig and the plasma cell marker CD138 are seen in spleens
|
|
• enlarged spleens in mice 550-600 days of age
|
|
• mice show some reduction in the germinal center B cell fraction at day 10 after primary and secondary immunization
|
|
• hyperplasia of B cells in the spleen and bone marrow at 550-600 days
|
|
• hyperplasia of plasma cells in the spleen and bone marrow at 550-600 days
• clonal or oligoclonal plasma cell expansions
|
|
• large numbers of cells expressing intracellular Ig and the plasma cell marker CD138 are seen in spleens
|
|
• enlarged spleens in mice 550-600 days of age
|
|
• enlarged spleens in mice 550-600 days of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• peripheral blood is deficient in eosinophils relative to wild-type (0.19% vs 1.85%)
• other non-eosinophilic circulating cell populations are unchanged in cell number and relative composition in mutants
|
|
• peripheral blood is deficient in eosinophils relative to wild-type (0.19% vs 1.85%)
• other non-eosinophilic circulating cell populations are unchanged in cell number and relative composition in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• plasma cell formation is severely impeded 10 days after primary and secondary immunization
|
|
• mice show increased numbers of germinal center B cells at day 10 after primary immunizations
|
|
• small, but significant, increase of the fraction of germinal center B cells in the S and G2 phases of the cell cycle
|
|
• reduction in total as well as sheep red blood cell-specific IgG1, but not IgM, antibodies 10 days after primary and secondary immunization
|
|
• plasma cell formation is severely impeded 10 days after primary and secondary immunization
|
|
• mice show increased numbers of germinal center B cells at day 10 after primary immunizations
|
|
• small, but significant, increase of the fraction of germinal center B cells in the S and G2 phases of the cell cycle
|
|
• reduction in total as well as sheep red blood cell-specific IgG1, but not IgM, antibodies 10 days after primary and secondary immunization
|
|
• shortened survival, with 40% survival at around 500 days of age
|
|
• mice succumb to a B cell-derived lymphoproliferative disease affecting spleen and lymph nodes, resembling human diffuse large B cell lymphoma
• mice develop clonal lymphomas consistent with activated B cell-diffuse large B cell lymphoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| non-Hodgkin lymphoma | DOID:0060060 |
OMIM:605027 |
J:167612 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
|
• 1-2 days after crosslinking with BCR, there are more cells is S phase than in wild-type B cell cultures
|
|
• B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
|
|
• B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
|
|
• cells on average have a longer lifespan than wild-type B cells
|
|
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
|
• B cell numbers are increased in spleens (130 x 106) compared to wild-type (56 x 106)
|
|
• B cell hyperplasia is observed, with a significantly expanded population of marginal zone B cells
|
|
• cells on average have a longer lifespan than wild-type B cells
|
|
• 1-2 days after crosslinking with BCR, there are less apoptotic cells than in purified wild-type B cell cultures
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal numbers of mature B cells including follicular and marginal zone B cells are produced
• spleens contain well-organized lymphoid architecture with normal follicles and distinct marginal zone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation
|
|
• mice are resistant to direct and passive MOG-induced experimental autoimmune encephalomyelitis
|
|
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells, but not dendritic cells or macrophages, are capable of inducing proliferation of CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch in vitro unlike wild-type cells
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation and instead undergo cell death
• mice are capable of inducing proliferation of memory T cells expressing Tg(Tcra2D2,Tcrb2D2)1Kuch unlike wild type mice
• mice are capable of inducing proliferation of Tg(Tcra2D2,Tcrb2D2)1Kuch T cells also deficient in Pdcd1 (Pdcd1tm1Hon) up to 71% or following treatment with anti-CTLA-4 antibodies up to 79% and proliferation is increased to 97% when both are used
• B cells induce peripheral tolerance by sensitizing T cells to antigen induced cell death in adoptive transfer experiments
|
|
• mice are resistant to direct and passive MOG-induced experimental autoimmune encephalomyelitis (EAE) and can confer some resistance upon adoptive transfer of B cells into wild-type micemice are resistant to direct and passive MOG-induced experimental encephalomyelitis (EAE) and can confer some resistance upon adoptive transfer of B cells into wild-type mice
• resistance to EAE is not affected by depletion of T regulatory cells
• however, mice inoculated with C57BL/6 spinal cord fluid develop EAE
|
|
• B cells, but not dendritic cells or macrophages, are capable of inducing proliferation of CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch in vitro unlike wild-type cells
• unlike in vitro, when CD4+ T cells containing Tg(Tcra2D2,Tcrb2D2)1Kuch are transferred into mice they fail to exhibit proliferation and instead undergo cell death
• mice are capable of inducing proliferation of memory T cells expressing Tg(Tcra2D2,Tcrb2D2)1Kuch unlike wild type mice
• mice are capable of inducing proliferation of Tg(Tcra2D2,Tcrb2D2)1Kuch T cells also deficient in Pdcd1 (Pdcd1tm1Hon) up to 71% or following treatment with anti-CTLA-4 antibodies up to 79% and proliferation is increased to 97% when both are used
• B cells induce peripheral tolerance by sensitizing T cells to antigen induced cell death in adoptive transfer experiments
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Renal abnormalities in Gt(ROSA)26Sortm1(Ptpn22*)Draw/Gt(ROSA)26Sor+ Cd19tm1(cre)Cgn/Cd19+ mice
|
• at 10 months
|
|
• at 10 months
|
|
• of age-dependent B cells
|
|
• in aged mice
|
|
• broad range of autoantibodies in aged mice
|
|
• in aged mice
|
|
• in aged mice with increased cellularity and mesangial matrix and infiltration of Mac1+ cells
|
|
• in aged mice with increased cellularity and mesangial matrix and infiltration of Mac1+ cells
|
|
• in aged mice
|
|
• at 10 months
|
|
• at 10 months
|
|
• of age-dependent B cells
|
|
• in aged mice
|
|
• at 10 months
|
|
• at 10 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• in the absence of tamoxifen no thymus abnormalities are detected
|
|
• treatment with tamoxifen at 12 and 24 months of age reverses thymus involution as measured by increase in thymus size and thymocyte numbers, and the presence of clearly defined cortical and medullary regions
• increase in the proliferation of thymic epithelial cells in mice treated at 12 and 24 months of age with tamoxifen compared to age matched controls
|
|
• treatment with tamoxifen at 12 and 24 months of age reverses thymus involution as measured by increase in thymus size and thymocyte numbers, and the presence of clearly defined cortical and medullary regions
• increase in the proliferation of thymic epithelial cells in mice treated at 12 and 24 months of age with tamoxifen compared to age matched controls
|
|
• increase in the number of naive T cells in the peripheral immune system in mice treated at 12 and 24 months of age with tamoxifen compared to age matched controls
|
|
• treatment with tamoxifen at 12 and 24 months of age reverses thymus involution as measured by increase in thymus size and thymocyte numbers, and the presence of clearly defined cortical and medullary regions
• increase in the proliferation of thymic epithelial cells in mice treated at 12 and 24 months of age with tamoxifen compared to age matched controls
|
|
• increase in the number of naive T cells in the peripheral immune system in mice treated at 12 and 24 months of age with tamoxifen compared to age matched controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• less pronounced than in Nhlh2tm2Thbr/Nhlh2tm2Thbr Tg(CMV-cre)1Cgn mice
|
|
|
• less pronounced than in Nhlh2tm2Thbr/Nhlh2tm2Thbr Tg(CMV-cre)1Cgn mice
|
|
• severe reduction in Pomc+ neurons
|
|
• increased visceral fat mass
• however, subcutaneous adipose weight is normal
|
|
|
• less pronounced than in Nhlh2tm2Thbr/Nhlh2tm2Thbr Tg(CMV-cre)1Cgn mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts exhibit diplo-chromosomes with unseparated arms unlike in control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• capsaicin infusion into striatum does not affect exploratory or motor behavior in Cre-activated mutants or controls
|
|
• infusion of capsaicin into striatum of results in stereotyped contralateral circling behavior within 5 minutes of delivery, while control mice without activation of Trpv1 show no effect
|
|
• infusion of high doses of capsaicin (5-10 um) into striatum results in dose-dependent excitotoxicity in neuronal cultures
• at doses sufficient to induce circling, no cell death is observed
|
|
• in layer 5 cortical slices, capsaicin induces action potentials while cells from Cre-negative animals show no response
• neurons in slices show dose-dependent depolarizing currents in response to capsaicin applied to the bath
• capsaicin applied acutely to single cells causes reproducible bursts of action potentials with increases in firing rate; frequency of firing is dependent on duration and concentration of capsaicin application
|
|
• infusion of high doses of capsaicin (5-10 um) into striatum results in dose-dependent excitotoxicity in neuronal cultures
• at doses sufficient to induce circling, no cell death is observed
|
|
• infusion of high doses of capsaicin (5-10 um) into striatum results in dose-dependent excitotoxicity in neuronal cultures
• at doses sufficient to induce circling, no cell death is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival of pIpC-treated mice is 99 days compared with 150 days for Gt(Rosa)26Sortm4(CAG-hsb5)Nki Gt(Rosa)26Sor+ Tg(Mx1-cre)1Cgn TgTn(pb-sb-GrOnc)#aGsva control mice
|
|
• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction
|
|
• in pIpC-treated mice
|
|
• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction
• however, pIpC-treated mice do not develop T cell lymphomas unlike in control mice
|
|
• in some pIpC-treated mice
|
|
• angiosarcoma in some pIpC-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• glucose clearance is increased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a decrease in survival with median survival of 116.5 days
|
|
• majority of pIpC treated mice (85%) develop an exclusively myeloid and primary acute leukemia phenotype
• 5% of mice remain in the chronic phase of the disease
• about 10% of mice develop an accelerated phase-like phenotype but with less than 20% blasts
• however, mice do not develop lymphoid leukemias
|
|
• in pIpC treated mice
|
|
• hemoglobin levels are decreased in pIpC treated mice
|
|
• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease
|
|
• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment
• increase in infiltration of tissues with both granulocytes and immature cells
|
|
• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils
|
|
• the myeloid progenitor compartment is expanded in pIpC treated mice, including the granulocyte monocyte progenitor compartment
|
|
• expansion of the lineage-negative (Lin-) bone marrow fraction in pIpC treated mice
• however, no differences are seen in total Lin-Sca+c-kit+ (LSK) numbers, long-term and short-term hematopoietic stem cell or multipotent progenitor proportions
|
|
• hematopoietic stem cells show an increased ability to serially replate compared to control cells
|
|
• in pIpC treated mice
|
|
• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease
|
|
• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment
• increase in infiltration of tissues with both granulocytes and immature cells
|
|
• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils
|
|
• in pIpC treated mice
|
|
• in pIpC treated mice
|
|
• in pIpC treated mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| chronic myeloid leukemia | DOID:8552 |
OMIM:608232 |
J:227558 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a median survival of 125.5 days
|
|
• 26% of mice treated with pIpC develop lymphoid acute leukemias
• 70% of mice treated with pIpC develop myeloid acute leukemias
• increase in infiltration of tissues with immature cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice die before 3 weeks
|
|
• slightly less so than in Gt(ROSA)26Sortm1(Gck)Ydor/Gt(ROSA)26Sor+ Tg(Ins2-cre)25Mgn mice
|
| N |
• islet architecture and beta cells are preserved in newborns
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Enlarged spleen in Gt(ROSA)26Sortm1(ITK/SYK)Jrld/Gt(ROSA)26Sor+ Tg(Cd4-cre)1Cwi/0 mice
|
• mice die by 30 weeks
|
| N |
• mice exhibit normal B cell morphology
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• mice exhibit profound T cell lymphoproliferative disorder unlike wild-type mice
|
|
• mice exhibit a decrease in mature peripheral T cells compared with wild-type mice
|
|
• at 20 weeks, spleens exhibit infiltration of medium to large-sized lymphoid cells with irregular nuclei, prominent nucleoli, and high mitotic rates suggesting neoplastic growth unlike in wild-type mice
|
|
• at 20 weeks
|
|
• the majority of CD4+ and CD8+ T cells exhibit an activated phenotype unlike wild-type cells
|
|
• in remaining T cells
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• at 12 weeks
|
|
• at 12 weeks
|
|
• at 20 weeks
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• mice exhibit profound T cell lymphoproliferative disorder unlike wild-type mice
|
|
• mice exhibit a decrease in mature peripheral T cells compared with wild-type mice
|
|
• at 20 weeks, spleens exhibit infiltration of medium to large-sized lymphoid cells with irregular nuclei, prominent nucleoli, and high mitotic rates suggesting neoplastic growth unlike in wild-type mice
|
|
• at 20 weeks
|
|
• the majority of CD4+ and CD8+ T cells exhibit an activated phenotype unlike wild-type cells
|
|
• in remaining T cells
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• in remaining T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice exhibit shortened lifespan
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
• tamoxifen treated mice exhibit accelerated formation of lung and pancreatic tumors compared to single Tg(RasE)290Biat transgenics
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
|
|
• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
|
|
• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unlike in wild-type mice, glucose and insulin levels are unresponsive to treatment with 3-iodothyronamine
|
|
• plasma insulin levels are 4- to 5-fold higher than in wild-type mice
• plasma insulin levels following administration of glucose increased 6.5-fold over basal levels compared to an increase of only 3-fold in similarly treated wild-type mice and peak insulin level achieved is 15-fold higher than in similarly treated wild-type mice
|
|
• glucose clearance is increased compared to in wild-type mice
• when fed a high fat diet, mice exhibit improved glucose tolerance and normal fasting blood glucose levels compared to wild-type mice
• unlike wild-type mice, treatment with SLIGRL does not alter plasma glucose levels
|
| N |
• despite altered glucose homeostasis, mice exhibit normal pancreatic islet cell size, number, histological appearance and cellular composition
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 80% of tamoxifen-injected mice develop tumors in the skin which immunohistochemistry suggests are skin-appendage tumors derived from sebaceous glands
• skin-appendage tumors develop when 4-OH tamoxifen is applied atopically onto the back of the skin; 98.3% of tumors show simultaneous activation of the three alleles
|
|
• 100% of mice develop lung and pancreatic cancers at between 8 and 12 weeks after tamoxifen injection
|
|
• pancreatic tumors of tamoxifen treated mice are intraepithelial neoplasias or pancreatic ductal adenocarcinomas
|
|
• pancreatic tumors of tamoxifen treated mice are intraepithelial neoplasias or pancreatic ductal adenocarcinomas
|
|
• 100% of mice develop lung and pancreatic cancers at between 8 and 12 weeks after tamoxifen injection
|
|
• lung tumors of tamoxifen treated mice are adenocarcinomas
|
|
• about 80% of tamoxifen-injected mice develop tumors in the skin which immunohistochemistry suggests are skin-appendage tumors derived from sebaceous glands
• skin-appendage tumors develop when 4-OH tamoxifen is applied atopically onto the back of the skin; 98.3% of tumors show simultaneous activation of the three alleles
|
|
• 100% of mice develop lung and pancreatic cancers at between 8 and 12 weeks after tamoxifen injection
|
|
• pancreatic tumors of tamoxifen treated mice are intraepithelial neoplasias or pancreatic ductal adenocarcinomas
|
|
• pancreatic tumors of tamoxifen treated mice are intraepithelial neoplasias or pancreatic ductal adenocarcinomas
|
|
• 100% of mice develop lung and pancreatic cancers at between 8 and 12 weeks after tamoxifen injection
|
|
• lung tumors of tamoxifen treated mice are adenocarcinomas
|
|
• about 80% of tamoxifen-injected mice develop tumors in the skin which immunohistochemistry suggests are skin-appendage tumors derived from sebaceous glands
• skin-appendage tumors develop when 4-OH tamoxifen is applied atopically onto the back of the skin; 98.3% of tumors show simultaneous activation of the three alleles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Prostate cancer progression in Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+, Tg(Pbsn-cre)4Prb/0 Ptentm1Mro/Pten+, and Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+ Ptentm1Mro/Pten+ mice
|
|
• at 6 months, mice exhibit atypical hyperplastic foci in the prostate lobes unlike control mice
|
|
|
• multifocal lesions at 9 months
|
|
|
• multifocal lesions at 9 months
|
|
|
• at 6 months, mice exhibit atypical hyperplastic foci in the prostate lobes unlike control mice
|
|
|
• multifocal lesions at 9 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Prostate cancer progression in Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+, Tg(Pbsn-cre)4Prb/0 Ptentm1Mro/Pten+, and Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sortm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor+ Ptentm1Mro/Pten+ mice
|
|
• 55% penetrance at 1 year
• multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized
|
|
|
• at 6 months
|
|
• frequently
|
|
|
• 55% penetrance at 1 year
• multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized
|
|
|
• at 6 months
|
|
|
• 55% penetrance at 1 year
• multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized
|
|
|
• at 6 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:184533 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within 4 to 5 days after treatment with tamoxifen at around age P21
|
|
|
• after treatment with tamoxifen at around age P21
|
|
|
• early in diplotene with some progression into metaphase
|
|
|
• after treatment with tamoxifen at around age P21
|
|
|
• after treatment with tamoxifen at around age P21
|
|
|
• early in diplotene with some progression into metaphase
|
|
|
• after treatment with tamoxifen at around age P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• at stage XII (pachytene/diplotene) in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• at stage XII (pachytene/diplotene) in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
|
|
• CD19+ B cells in tamoxifen-treated mice
• B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
• however, cell counts return to baseline after 2 weeks and a second application of tamoxifen does not result in another wave of B cell expansion
|
|
• massive expansion in tamoxifen-treated mice
|
|
• massive expansion in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
• however, T cell numbers decrease 8 days after tamoxifen application
|
|
• vigorous degranulation when T cells from tamoxifen-treated mice are exposed to LMP1-transduced B cells in vitro
|
|
• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
|
|
• CD19+ B cells in tamoxifen-treated mice
• B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
• however, cell counts return to baseline after 2 weeks and a second application of tamoxifen does not result in another wave of B cell expansion
|
|
• massive expansion in tamoxifen-treated mice
|
|
• massive expansion in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
• however, T cell numbers decrease 8 days after tamoxifen application
|
|
• vigorous degranulation when T cells from tamoxifen-treated mice are exposed to LMP1-transduced B cells in vitro
|
|
• with B cell blasts outnumbering normal splenic B cells 20-fold in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryonic stem cells treated with tamoxifen exhibit reduced ability to re-form colonies compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are runted prior to weaning
|
|
• mice exhibit lower body weights throughout life
• mice treated with an alpha IL-1R blocking antibody show weight gain
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli
• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates
• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes
|
|
• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes
|
|
• decrease in blood lymphocytes
|
|
• B cell numbers are modestly decreased in the lymph nodes
|
|
• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates
• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes
|
|
• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated
• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged
|
|
• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint
• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling
|
|
• sick mice exhibit enlarged spleen
|
|
• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli
• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates
• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes
|
|
• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes
|
|
• decrease in blood lymphocytes
|
|
• B cell numbers are modestly decreased in the lymph nodes
|
|
• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates
• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes
• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes
|
|
• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated
• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged
|
|
• sick mice exhibit enlarged lymph nodes
|
|
• mice exhibit systemic inflammation, with nearly all tissues showing neutrophilic infiltration
|
|
• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa
|
|
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
|
|
• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes
|
|
• some mice exhibit glomeruli with only thickened membranes
|
|
• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes
|
|
• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint
• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling
|
|
• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| primary immunodeficiency disease | DOID:612 |
OMIM:242850 OMIM:PS300755 |
J:260047 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neutrophilic inflammation is not apparent
|
| N |
• mice exhibit normal joints
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numerous anomalies are evident in the branching pattern of the facial nerve
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• observed in about 18% of viable embryos collected at 14.5 days post coitus
|
|
• observed with around 4% frequency in viable embryos collected at 14.5 days post coitus
|
|
• observed in about 18% of viable embryos collected at 14.5 days post coitus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Thymic aplasia, nasal malformations, and eye, pharyngeal and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Foxg1tm1(cre)Skm/Foxg1+ mice and microcephaly, ocular and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Tg(Pax2-cre)1Akg/0 mice
|
• hypoplastic to varying degrees, but enlarged in two instances
|
|
• enlarged at E14.5
|
|
• enlarged at E14.5
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some embryos have open hindbrain neuropores, but open posterior neuropores (spina bifida) are not seen
|
|
• some embryos have open hindbrain neuropores, but open posterior neuropores (spina bifida) are not seen
|
|
• observed with 10% frequency in viable embryos collected at 14.5 days post coitus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• observed in about 40% of embryos collected at 14.5 days post coitus
|
|
• observed in about 40% of embryos collected at 14.5 days post coitus
|
|
• observed with 20% frequency at 14.5 days post coitus; no embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• marginally fewer than expected mice are present at 3 weeks
|
|
• the area of columnar proliferating chondrocytes is larger than in wild-type mice
|
|
• prehypertrophic and hypertrophic zones are reduced in size compared to in wild-type mice
|
|
• in 2 of 30 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• upon induction with 4-hydroxytamoxifen (4-OHTA), 2/4 mice develop regional keratoacanthomas at site of drug application within 8 weeks
|
|
• 2/4 induced animals acquire lymphoma
|
|
• 2/4 induced animals acquire lung tumors
|
|
• upon induction with 4-hydroxytamoxifen (4-OHTA), 2/4 mice develop regional keratoacanthomas at site of drug application within 8 weeks
|
|
• 2/4 induced animals acquire lung tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen, cell survival of mouse embryonic fibroblasts following treatment with ionizing radiation is slightly decreased compared to in wild-type cells
|
|
• following treatment with tamoxifen, mouse embryonic fibroblasts exhibit a modest decrease in proliferation compared to wild-type
|
|
• following treatment with tamoxifen, the number of chromosome abnormalities in mouse embryonic fibroblasts is increased compared to in wild-type cells
|
|
• following treatment with tamoxifen, cell survival of mouse embryonic fibroblasts following treatment with ionizing radiation is slightly decreased compared to in wild-type cells
|
|
• following treatment with tamoxifen, the number of chromosome abnormalities in mouse embryonic fibroblasts is increased compared to in wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hindlimbs from some E18.5 embryos have multiple posterior distal bifurcations (1/4)
• forelimbs from some E18.5 embryos have large nubs in the posterior (3/4)
|
|
• hindlimbs from some E18.5 embryos have posterior polydactyly (3/4)
|
|
• forelimbs from some E18.5 embryos have preaxial polydactyly (1/4)
|
|
• hindlimbs from some E18.5 embryos have multiple posterior distal bifurcations (1/4)
• forelimbs from some E18.5 embryos have large nubs in the posterior (3/4)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen, mouse embryonic fibroblasts exhibit a decrease in proliferation compared to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the nasal domain of retinal axon termination zone is expanded anteriorly compared to in wild-type mice
|
|
• the nasal domain of retinal axon termination zone is expanded anteriorly compared to in wild-type mice
|
| N |
• retinal development, size, and patterning are normal
|
|
• the nasal domain of retinal axon termination zone is expanded anteriorly compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• animals do not exhibit any signs of self-mutilation or taste response deficits
• animals have normal mechanosensory responses following nerve ligation or sensitization by inflammation; responses in assays for touch and pinch assays are identical to controls
• rotarod results are normal, indicating no loss of proprioceptive function
|
|
• responses to capsaicin and mustard oil in eye wipe and paw injection paradigms are eliminated
• animals display no 'wet-dog shakes' in response to icilin injection which gives perception of cooling, whereas controls show robust characteristic responses
|
|
• mice are insensitive to noxious heat compared to controls (animals do not display protective thermosensory responses in hot plate paw withdrawal or tail-flick assays)
• mice show no reaction to a cold plate assay or preference in a 2-temperature choice test (30 C vs 5 C)
|
| N |
• distribution and arrangement of dorsal horn interneurons is not significantly different from wild-type animals
• recordings from sciatic nerve in response to stimulation of the foot (by brush, von Frey microfilaments, or vibration) are not different than in controls
• rotarod results are normal, indicating no loss of proprioceptive function
|
|
• mutants have reduced numbers of TRPV2-containing sensory neurons
|
|
• in response to IP injection of capsaicin, mice do not exhibit the profound hypothermia that is shown by treated controls
• mutants are unable to maintain their body temperature than wild-type controls when the environmental temperature is changed
• animals exhibit a greater hypothermic response than wild-type upon antigen injection, with slower re-establishment of normal resting temperature
• animals show a greater temperature change in response to mild fever induced by Il-1beta injection relative to wild-type
|
|
• responses to ATP, prostaglandins, bradykinin, histamine and serotonin are lost in mutants; significant loss of neurogenic inflammation is observed, and significantly less inflammation occurs in response to carageenan challenge
|
|
• mutants display complete loss of behavioral responses to injection of pruritogenic compounds
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• epicardial cells exhibit premature smooth muscle cell differentiation and fail to invade into the right ventricular myocardium unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when given tamoxifen at E13.5 or E14. the hemisphere phenotype is more severe than in double mutants that do not express Cre
|
|
• when given tamoxifen at E13.5 or E14. the vermis phenotype is more severe than in double mutants that do not express Cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• semilunar valves have reduced endocardial-derived mesenchyme
• 2-fold increase in EdU-incorporated mesenchymal cells, indicating increased proliferation of cushion mesenchyme
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
• however, mitochondria in the distal dopamine axons are morphologically spared
|
|
• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• lineage-tracing analysis showed no apparent defects in cranial and cardiac neural crest cell migration
|
| N |
• lineage-tracing analysis showed no apparent defects in cranial and cardiac neural crest cell migration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double heterozygotes are viable to E18.0 but no live mice are recovered
|
|
• oligodendrocytes cannot be detected in mutant embryos examined from
E12.5-18
|
|
• at E10.0, few motor neurons are detectable in the ventral spinal cord compared to wild-type; this result is consistent from E10.5-14
|
|
• oligodendrocytes cannot be detected in mutant embryos examined from
E12.5-18
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• partial rescue of ribbon loss observed Mafbtm1.1Good/Mafbtm1Jeng Tg(Neurog1-cre)1Jejo mice
|
|
• partial rescue of synaptic defects observed Mafbtm1.1Good/Mafbtm1Jeng Tg(Neurog1-cre)1Jejo mice
|
|
• partial rescue of ribbon loss observed Mafbtm1.1Good/Mafbtm1Jeng Tg(Neurog1-cre)1Jejo mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• small kidney in mice induced with doxycycline from E14.5 until the end of the experiment
• however, cap mesenchyme differentiates normally in doxycycline induced mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice develop kidney tumors within the first 2 weeks of life following doxycycline (Dox) induction during embryonic development at E0, E14.5 or E18.5
• tumors resemble Wilms tumor
• mice treated with doxycycline at P10 do not develop tumors
|
|
• mice treated with doxycycline at P10 develop cystic kidneys
|
|
• all mice develop kidney tumors within the first 2 weeks of life following doxycycline (Dox) induction during embryonic development at E0, E14.5 or E18.5
• tumors resemble Wilms tumor
• mice treated with doxycycline at P10 do not develop tumors
|
|
• doxycycline induced mice exhibit persistent proliferation of cap mesenchyme cells in adults
• however, cap mesenchyme cells within tumors retain a differentiation capacity that recapitulates normal kidney development
|
|
• timing of kidney development is prolonged in doxycycline induced mice, with sustaining proliferation of the cap mesenchyme cells into adulthood
|
|
• mice treated with doxycycline at P10 develop cystic kidneys
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| nephroblastoma | DOID:2154 |
OMIM:194070 |
J:211179 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop hydronephrosis following doxycycline induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• loss of Nr0b1 does not impact ability of zona glomerusa cells to contribute to the inner zona fasciculata even at 8 months of age; postnatal zonation and lineage conversion in the adrenal gland are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at a median age of 26 days
|
|
• mice show progressive weight loss after 2 weeks of age
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice exhibit an atrophied thymus
|
|
• mice exhibit an atrophied thymus
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice show thrombocytopenia after 2 weeks of age
|
|
• mice show an increase in the frequency of CD11c+dendritic cells in the bone marrow and spleen, with expansion particularly in the atrophied thymus
• mice show histiocytic infiltrate in the spleen, liver, lung and intestines and an increase in frequency of CD11b+Gr1+ cells in the blood, bone marrow, liver, and spleen
|
|
• frequency of B220+ B lymphocytes is decreased
|
|
• frequency of CD3+ T lymphocytes is decreased
|
|
• atrophied thymus shows a deficit of CD4-CD8-CD25+ committed T cell progenitors
|
|
• atrophied thymus shows a deficit of CD4+CD8+ double-positive cells
|
|
• mice show leukocytosis after 2 weeks of age
|
|
• mice show monocytosis after 2 weeks of age
|
|
• moribund mice show a reduction hematopoietic stem cells (LSK CD150+CD48-) and multipotent progenitors (LSK CD150-CD48+) in the bone marrow and spleen
|
|
• mice exhibit an atrophied thymus
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice show an increase in the frequency of CD11c+dendritic cells in the bone marrow and spleen, with expansion particularly in the atrophied thymus
• mice show histiocytic infiltrate in the spleen, liver, lung and intestines and an increase in frequency of CD11b+Gr1+ cells in the blood, bone marrow, liver, and spleen
|
|
• frequency of B220+ B lymphocytes is decreased
|
|
• frequency of CD3+ T lymphocytes is decreased
|
|
• atrophied thymus shows a deficit of CD4-CD8-CD25+ committed T cell progenitors
|
|
• atrophied thymus shows a deficit of CD4+CD8+ double-positive cells
|
|
• mice show leukocytosis after 2 weeks of age
|
|
• mice show monocytosis after 2 weeks of age
|
|
• mice develop a juvenile myelomonocytic leukemia-like disease
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| juvenile myelomonocytic leukemia | DOID:0050458 |
OMIM:607785 |
J:247853 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23
|
|
• pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• block at the progression at the conversion of A spermatogonia to A1 following chronic treatment with tamoxifen
|
|
|
• sperm depletion occurs after chronic administration of tamoxifen
|
|
|
• sperm depletion occurs after chronic administration of tamoxifen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• skin grafts on nude mice treated with doxycycline exhibit stunted hair growth unlike control grafts
|
|
• doxycycline-treated mice exhibit multi-layered epithelium unlike control mice
|
|
• skin grafts on nude mice treated with doxycycline exhibit hyperkeratosis unlike control grafts
|
|
• skin grafts on nude mice treated with doxycycline exhibit hyperkeratosis unlike control grafts
|
|
• 8 days after doxycycline treatment
|
|
• 8 days after doxycycline treatment
|
|
• skin from doxycycline-treated mice exhibit a greater than 5-fold increase in the number of colony-forming cells compared with skin from control mice
|
|
• in nude mice receiving skin grafts and treated with doxycycline
|
|
• thickened and dysplastic in doxycycline-treated mice
|
|
• in nude mice receiving skin grafts and treated with doxycycline
|
|
• doxycycline-treated mice exhibit increased cell proliferation of basal cells and an extension of the proliferative domain into the suprabasal layers of back skin compared with control mice
|
|
• thickened and dysplastic in doxycycline-treated mice
|
|
• thickened and dysplastic in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop cystic kidneys when transgene expression is induced with doxycycline early in embryonic development or in adult mice
|
|
• mice develop cystic kidneys when transgene expression is induced with doxycycline early in embryonic development or in adult mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 4 of 11 mice administered doxycycline at 3 months of age develop prostate tumors with age
• tumors include adenocarcinomas, sarcomatoid carcinomas (epithelial-mesenchymal transition-like epithelial tumor), and stromal-type tumors
|
|
|
• 4 of 11 mice administered doxycycline at 3 months of age develop prostate tumors with age
• tumors include adenocarcinomas, sarcomatoid carcinomas (epithelial-mesenchymal transition-like epithelial tumor), and stromal-type tumors
|
|
|
• 4 of 11 mice administered doxycycline at 3 months of age develop prostate tumors with age
• tumors include adenocarcinomas, sarcomatoid carcinomas (epithelial-mesenchymal transition-like epithelial tumor), and stromal-type tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:222916 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no kidney pathology is seen in mice induced with doxycycline
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normalized muscle fiber size compared with Mnx1tm4(cre)Tmj heterozygotes
|
| N |
• mice exhibit normalized endplate size compared with Mnx1tm4(cre)Tmj heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal numbers of epicardium-derived cells (EPDCs) and epicardial epithelial-mesenchymal transition (EMT) occurs normally
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when tamoxifen is administered at E10.5, rhombomere 1 (r1) is reduced in size in mutants at E12.5
• anterior r1 cells contribute to more lateral regions of vermis than normal
|
|
• when tamoxifen is administered at E10.5, mesencephalon is reduced in size at E12.5 relative to normal
• marked cells in posterior mesencephalon do not expand normally
|
|
• when tamoxifen is administered at E10.5, size of marked domain is smaller than wild-type at E16.5
• in adults, marked domain in tectum is greatly reduced compared to wild-type; marked domain is restricted to remaining region of inferior colliculus
|
|
• when tamoxifen is administered at E10.5, size of marked cell population is wider in mutants than in controls at E16.5
• in adults, marked domain is broader than normal
|
|
• in adults, vermis is reduced in size
|
|
• when tamoxifen is administered at E10.5, rhombomere 1 (r1) is reduced in size in mutants at E12.5
• anterior r1 cells contribute to more lateral regions of vermis than normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E13.5 embryos
• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions
• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue
• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels
|
|
• in E13.5 embryos
• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions
• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue
• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos exposed to tamoxifen at E10.5-12.5 show some blood-filled dermal lymphatic vessels
• embryos exposed to tamoxifen show reduced number of superficial vessels (X-gal stained); severity of reduction increases with early tamoxifen treatment
• tamoxifen treatment at E10.5 or E11.5 results in severely reduced lymphatic endothelial cell numbers and lack of lymphatic vessels
• embryos exposed to tamoxifen at E10.5 or 11.5 display drastically mispatterned lymph sacs that are reduced in size compared to controls
• when tamoxifen exposure occurs at E13.5, few embryos show any lymphatic defects, while exposure later in development or postnatally causes no obvious defects despite reduction in Nr2f2 expression in LECs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the ventral pancreas fails to form at E11.5 with the precursor cells reverting to an intestinal epithelial fate
• growth retardation of the dorsal epithelial bud is evident at E11.5
• the dorsal epithelial bud is significantly smaller at E12.5
• at E17.5, the dorsal pancreatic epithelium is a truncated, poorly branched, duct like structure without islet or acinar tissues
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic progenitor cells (GFP +ve) form cystic structures, not narrow, branched structures, that lack endocrine or acinar marker expression with tamoxifen treatment (2 mg) at E9.5 or 11.5
• treatment at E13.5 or 15.5 blocks islet differentiation, but some exocrine differentiation occurs, with labeled cells integrating into normal acini and ducts
• treatment with 0.5 mg tamoxifen at E9.5 still results in formation of abnormal cystic tubules as seen with the higher dose
• Notch 1 activation at E13.5 results in most GFP +ve cells adopting a ductal, rather than acinar, fate; activation at E15.5 reverses the proportions with most cells taking an acinar fate
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced proliferation in the mesoderm compartment of both paraxial mesoderm and ectopic ventral mass
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos do not develop intramyocardial coronary arteries
|
|
• at E11.5, endocardial cells cannot respond to Vegf120 and fail to migrate, sprout, and form endothelial networks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hypoplastic, particularly the trigeminal ganglion
|
|
• maxillary branch is consistently narrower than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced
|
|
• at E9.5, cardiac NCCs migrate to the developing caudal pharyngeal arches of mutant embryos in numbers comparable to those of wild-type embryos; however, at E11.5, NCCs fail to invaginate on the right side of the proximal aortic sac at the level of its connection with the 6th aortic arch arteries
• as a result, the conotruncal cushions remain oriented laterally relative to one another
|
|
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced
|
|
• homozygotes exhibit abnormal NCC behavior during outflow tract remodeling
|
|
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced
|
|
• at E9.5, cardiac NCCs migrate to the developing caudal pharyngeal arches of mutant embryos in numbers comparable to those of wild-type embryos; however, at E11.5, NCCs fail to invaginate on the right side of the proximal aortic sac at the level of its connection with the 6th aortic arch arteries
• as a result, the conotruncal cushions remain oriented laterally relative to one another
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• E17.5 embryos often have hemorrhaging in the lung
|
|
• at E12, moderate increases in apoptosis are observed in the primary bronchi of both lungs
• cell death extended farther into the medial and accessory branches and there was a small area of ectopic death observed in the mesenchyme of either the vestigial rostral lobe or at the distal tip of the accessory lobe
|
|
• all lobes exhibit reduced branching following outgrowth of the initial branch that established the lobe
• mesenchymal protrusions without an accompanying epithelial branch are occasionally observed during embryonic development
• such protrusions are observed only in the right lung in positions that correspond to lobes
|
|
• at E17.5, mutant lobes are smaller and much flatter than control lobes
|
|
• at E12.5, the accessory lobe is reduced in size and often misshapen
|
|
• most E11.5 embryos have a reduction or absence of the nascent rostral lobe
• at E12.5, the rostral lobe is absent in the majority of mice
|
|
• at E12.5, the medial lobe is reduced in size and often misshapen
|
|
• at E17.5, mutant lobes are smaller than control lobes
|
|
• at E12.5, mutant lungs are smaller than control lungs
|
|
• at E17.5, mutant lungs are severely hypoplastic
|
|
• E17.5 embryos often have hemorrhaging in the lung
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all lateral hypothalamic area (LHA) Nts +ve neurons treated with leptin become hyperpolarized; in controls, about 20% of wild-type LHA Nts +ve neurons treated with leptin while about 60% depolarize upon leptin treatment
• this indicates that deletion of Lepr from Lepr, Nts +ve neurons abrogates the direct depolarization response
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice show a very large increase in plasma desmosterol level
• liver, brain, and heart tissue desmosterol levels are elevated in tamoxifen-treated mice
• however, liver, brain and heart tissue cholesterol levels in tamoxifen-treated mice are normal
|
|
• mice treated with tamoxifen at 4-5 weeks of age show an early decline and stable decrease in plasma cholesterol
• however, cholesterol content of liver, brain, and heart is normal
|
|
• bile shows elevated desmosterol levels in tamoxifen-treated mice
• tamoxifen-treated mice show lower biliary cholesterol level
|
|
• bile shows elevated desmosterol levels in tamoxifen-treated mice
• tamoxifen-treated mice show lower biliary cholesterol level
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| desmosterolosis | DOID:0070654 |
OMIM:602398 |
J:304449 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• maxillary processes are slightly reduced at E10.5
|
|
• frontonasal prominence is slightly reduced at E10.5
• cranial neural crest (CNC) cell participation in the frontonasal prominence is markedly reduced
• however, neural tube formation is normal
|
|
• maxillary processes are slightly reduced at E10.5
|
|
• maxillary processes are slightly reduced at E10.5
|
|
• maxillary processes are slightly reduced at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E9.5, a 4-fold increase in apoptosis is detected in the neural crest cells (NCCs) of the facial mesenchyme
• at E10.5, apoptosis is significantly increased in both the medial nasal prominences (MNP) and lateral nasal prominences (LNP) and the olfactory pit
|
|
• at E9.5, a 4-fold increase in apoptosis is detected in the neural crest cells (NCCs) of the facial mesenchyme
• at E10.5, apoptosis is significantly increased in both the medial nasal prominences (MNP) and lateral nasal prominences (LNP) and the olfactory pit
|
|
• at E9.5, but not at E8.5, NCC proliferation is significantly reduced in the facial mesenchyme
• at E10.5, cell proliferation is significantly reduced in the olfactory pit and the lateral nasal prominences (LNP), but not in the medial nasal prominences (MNP)
|
|
• at E8.5, a 3-fold increase in apoptosis is detected in the anterior neuroepithelium of the cranial neural folds, including the anterior neural ridge (ANR); however, no elevated apoptosis is observed in the neural crest cells (NCCs) at this age
|
|
• at E9.5, a 4-fold increase in apoptosis is detected in the neural crest cells (NCCs) of the facial mesenchyme
• at E10.5, apoptosis is significantly increased in both the medial nasal prominences (MNP) and lateral nasal prominences (LNP) and the olfactory pit
|
|
• at E9.5, a 4-fold increase in apoptosis is detected in the neural crest cells (NCCs) of the facial mesenchyme
• at E10.5, apoptosis is significantly increased in both the medial nasal prominences (MNP) and lateral nasal prominences (LNP) and the olfactory pit
|
|
• at E8.5, a 3-fold increase in apoptosis is detected in the anterior neuroepithelium of the cranial neural folds, including the anterior neural ridge (ANR); however, no elevated apoptosis is observed in the neural crest cells (NCCs) at this age
|
|
• at E9.5, but not at E8.5, NCC proliferation is significantly reduced in the facial mesenchyme
• at E10.5, cell proliferation is significantly reduced in the olfactory pit and the lateral nasal prominences (LNP), but not in the medial nasal prominences (MNP)
|
|
• at E10.5, apoptosis is significantly increased whereas cell proliferation is significantly reduced in the olfactory pit
|
|
• at E9.5, a 4-fold increase in apoptosis is detected in the neural crest cells (NCCs) of the facial mesenchyme
• at E10.5, apoptosis is significantly increased in both the medial nasal prominences (MNP) and lateral nasal prominences (LNP) and the olfactory pit
|
|
• at E10.5, apoptosis is significantly increased whereas cell proliferation is significantly reduced in the olfactory pit
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the size of the first branchial arch is normal at E10.5
|
| N |
• the size of the first branchial arch is normal at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die soon after birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mouse embryonic fibroblasts increased expression of VL30-pro endogenous retroviruses (ERV) elements compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 3 months of age tamoxifen treated mice show increased organ weight to body weight ratios
|
|
• following tamoxifen treatment at P1-P5
• difference in weight increases progressively with age reaching approximately a 40% decrease by 6 months of age
|
|
• decreased junctional density in tamoxifen treated mice, possibly secondary to edema
|
|
• wider spaces at 6 months of age in tamoxifen treated mice
|
|
• modest decrease in WT-1+ podocyte densities in tamoxifen treated mice
|
|
• increased glomerular volume in tamoxifen treated mice at 6 months of age
• in tamoxifen treated mice glomerular endothelial cells become swollen and subendothelial thickening is seen
|
|
• glomerular loops show reduced fenestrae in tamoxifen treated mice
|
|
• expression analysis indicates reduced ENOS activity in renal microvasculature from tamoxifen treated mice at 3 months of age
|
|
• elevated albumin to creatinine ratio in the urine in tamoxifen treated mice
|
|
• progressive, age-related dysfunction in tamoxifen treated mice
|
|
• in tamoxifen treated mice at 6 months of age
|
|
• tubulointerstitial edema in tamoxifen treated mice
|
|
• in tamoxifen treated mice
|
|
• in tamoxifen treated mice
|
|
• increased wet weights of multiple tissues, including the kidneys, liver, lung, and heart in tamoxifen treated mice
|
|
• glomerular loops show reduced fenestrae in tamoxifen treated mice
|
|
• decreased junctional density in tamoxifen treated mice, possibly secondary to edema
|
|
• increased Evans Blue dye extravasation from kidney vessels in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice express cre in all mineralcorticoid target tissues, as determined by reporter expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• knots of retinal ganglion cell axons are observed, consistent with the small degree of rescue
|
|
• the BAC Crx-Atoh7 (Crx-Math5) construct shows some rescue of retinal axons and prevention of fasciculation defects in double mutants compared to Atoh7 homozygotes; level of rescue is lower than that seen in Atoh7-null homozygotes crossed to the conventional transgenic Atoh7 mice (Tg(Crx-Atoh7,-cre)251Gla)
• rescue is less pronounced with successive generations
|
|
• knots of retinal ganglion cell axons are observed, consistent with the small degree of rescue
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals much thinner optic nerves relative to controls
|
|
• in some animals, severe pathfinding defects are observed as the optic nerve exits the retina, forming a knot-like structure
|
|
• cell death is increased relative to Atoh7-null homozygotes with most dying cells observed in the ganglion cell layer (GCL)
|
|
• the transgenic Crx-Atoh7 (Math5) construct shows variable rescue of retinal axons and prevention of fasciculation defects in double mutants compared to Atoh7-null homozygotes
• rescue is less pronounced with successive generations
|
|
• animals much thinner optic nerves relative to controls
|
|
• in some animals, severe pathfinding defects are observed as the optic nerve exits the retina, forming a knot-like structure
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike single Wnk1 homozygotes, heart morphology is grossly normal
|
|
• the incidence of abnormal embryos is increased compared to controls indicating only a partial rescue
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged maxillae are comprised of neural crest-derived mesenchyme
|
|
• the depth of the migratory mesencephalic neural crest streams is far greater than in wild-type embryos
• cells rostral to the trigeminal ganglion are seen in a region that should normally be clear of neural crest cells
|
|
• E9.25 cranial tissues show an increase in the proportion of neural crest cells
|
|
• E9.25 cranial tissues show an increase in the proportion of neural crest cells
|
|
• the depth of the migratory mesencephalic neural crest streams is far greater than in wild-type embryos
• cells rostral to the trigeminal ganglion are seen in a region that should normally be clear of neural crest cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal contextual fear conditioning and prepulse mediated inhibition of acoustic startle reflex
|
|
• 5HT+ axon varicosities are enlarged compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the lethal inflammatory phenotype is completely rescued
|
| N |
• the lethal inflammatory phenotype is completely rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• skin lesions are not seen unlike in mutant mice lacking Gt(ROSA)26Sortm1(Ctnnb1)Kem
|
|
• broad stripes of hair loss are seen
• loss is followed by regrowth
|
|
• at P14; however, mice catch up with littermate controls with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 83-84% of satellite cells are ablated in the right tibialis anterior muscle after 5 doses of tamoxifen and 5days after muscle damage induced by BaCl2 injection
|
|
• reduced fibroblast expansion by 52% 5 days after muscle injury in tamoxifen treated mice
|
|
• 89% reduction in regenerating myofibers 5 days after muscle injury in tamoxifen treated mice
• muscle regeneration dramatically impaired 28 days after injury
• right tibialis anterior muscle entirely fibrotic at 28 days and uninjured left tibialis anterior is reduced by 38%
• similar result when damage induced with cardiotoxin, no recovery after 56 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Peyers patches are hypocellular and exhibit B-cell lymphopenia
|
|
• Peyers patches are small in size in P21-P24 mice but have normal architecture
|
|
• mice develop intestinal inflammation in both the proximal and mid-colon by P26-29
• however, no inflammation is seen at earlier time points on in the small intestine
|
|
• mature B-lymphocytes are reduced in Peyers patches and are enriched in the spleen
|
|
• the proportion of total B-lymphocytes in Peyers patches is decreased to about 80% of levels seen in controls, indicating a 3.6-fold reduction in the number of B cells
• mice show a decrease of B-lymphocytes in the germinal centers of spleens and a decrease of B-lymphocytes within the marginal zones
• however, no differences in pre/pro-B lymphocyte and mature B lymphocyte populations at P21 in the bone marrow
|
|
• mice show a decrease of B-lymphocytes in the germinal centers of spleens
|
|
• mice exhibit splenic lymphopenia
|
|
• mice show a decrease of B-lymphocytes within the marginal zones
|
|
• spleens in P21-P24 mice are smaller in size
|
|
• spleens weigh less than those of controls as a proportion of the total body weight
|
|
• decrease in the proportion of total (B220+) B-lymphocytes and in the numbers of total B lymphocytes in spleens
• increase in the proportion of mature B-lymphocytes in the spleen, although numbers are decreased
|
|
• secretory IgA is decreased in the small intestine
• however, no differences in secretory IgA are seen in the nasal airway lavage or bronchoalveolar lavage and no differences in small bowel luminal IgM levels are seen
|
|
• Peyers patches are hypocellular and exhibit B-cell lymphopenia
|
|
• Peyers patches are small in size in P21-P24 mice but have normal architecture
|
|
• mice develop intestinal inflammation in both the proximal and mid-colon by P26-29
• however, no inflammation is seen at earlier time points on in the small intestine
|
|
• mature B-lymphocytes are reduced in Peyers patches and are enriched in the spleen
|
|
• the proportion of total B-lymphocytes in Peyers patches is decreased to about 80% of levels seen in controls, indicating a 3.6-fold reduction in the number of B cells
• mice show a decrease of B-lymphocytes in the germinal centers of spleens and a decrease of B-lymphocytes within the marginal zones
• however, no differences in pre/pro-B lymphocyte and mature B lymphocyte populations at P21 in the bone marrow
|
|
• mice show a decrease of B-lymphocytes in the germinal centers of spleens
|
|
• mice exhibit splenic lymphopenia
|
|
• mice show a decrease of B-lymphocytes within the marginal zones
|
|
• spleens in P21-P24 mice are smaller in size
|
|
• spleens weigh less than those of controls as a proportion of the total body weight
|
|
• decrease in the proportion of total (B220+) B-lymphocytes and in the numbers of total B lymphocytes in spleens
• increase in the proportion of mature B-lymphocytes in the spleen, although numbers are decreased
|
|
• secretory IgA is decreased in the small intestine
• however, no differences in secretory IgA are seen in the nasal airway lavage or bronchoalveolar lavage and no differences in small bowel luminal IgM levels are seen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Hirschsprung's disease | DOID:10487 |
OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644 |
J:233811 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E14.5 embryos consist of a head attached to internal organs including lung, liver and intestine while the urogenital system and mesoderm-derived tissues making up the body wall are highly underdeveloped or absent
|
|
• truncated tail bud region at E9.5
|
|
• truncated tail bud region at E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with tamoxifen treatment at E12.5, presence of a single copy of Spry1 only marginally improves the hypoplasia observed at E19.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following induction of Cre-mediated recombination by TAM treatment at 3 weeks of age (1st telogen), mice show a noticeable hair-graying phenotype by the 2nd telogen; hair graying persists through the next hair cycle (3rd telogen), unlike in control mice
|
|
• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles that contain fewer differentiated melanocytes in the bulb by anagen IV
|
|
• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles unlike control mice
|
|
• following TAM treatment at 3 weeks of age (1st telogen), >65% of hair shafts lack melanin, leading to a hair-graying phenotype at the 2nd and 3rd telogen
|
|
• following TAM treatment at 3 weeks of age (1st telogen), melanocyte stem cells (McSCs) in unpigmented hair follicles show less BrdU incorporation than those in pigmented hair follicles of control mice at anagen III
|
|
• following induction of Cre-mediated recombination by TAM treatment at 3 weeks of age (1st telogen), mice show a noticeable hair-graying phenotype by the 2nd telogen; hair graying persists through the next hair cycle (3rd telogen), unlike in control mice
|
|
• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles that contain fewer differentiated melanocytes in the bulb by anagen IV
|
|
• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles unlike control mice
|
|
• following TAM treatment at 3 weeks of age (1st telogen), >65% of hair shafts lack melanin, leading to a hair-graying phenotype at the 2nd and 3rd telogen
|
|
• following TAM treatment at 3 weeks of age (1st telogen), unpigmented hair follicles contain fewer differentiated melanocytes in the bulb by anagen IV, as shown by a decreased number of tomato+ melanocytes expressing differentiation markers Dct, MITF, and S100
• % of apoptotic (Casp3+) bulb melanocytes is significantly increased relative to that in control mice at anagen VI
|
|
• following TAM treatment at 3 weeks of age (1st telogen), melanocyte stem cells (McSCs) in unpigmented hair follicles show less BrdU incorporation than those in pigmented hair follicles of control mice at anagen III
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E8.5 embryos have a sac-like structure composed of 2 layers where the outer layer is reminiscent of the visceral endoderm and the inner layer has characteristics of a pseudostratified epithelium
|
|
• expression analysis indicates failure to gastrulate
|
|
• formation of proper embryonic structures is incomplete
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E13.5, alpha-actinin staining showed that cardiac myocytes are separated from the tdTomato positive cNCCs in the OFT cushion
• by E15.5, far fewer cardiomyocytes are in contact with tdTomato positive cNCCs in the OFT cushion, indicating impaired muscularization
|
|
• by E15.5, cNCCs persist as a fibrous outlet septum in the setting of DORV
|
|
• 12.7% of explanted cultured cardiac neural crest cells (cNCCs) make cell-cell contacts versus 8.5% of control cNCCs; strikingly, 81% of those contacts fail to separate within 2 h versus only 31.2% in control cNCCs, suggesting increased cell-cell adhesion
|
|
• at E9.5, fewer tdTomato-labeled cNCCs are detected in the developing outflow tract (OFT) relative to control embryos, suggesting a delay in cNCC migration
• at E10.5, a nearly complete absence of tdTomato cNCCs is seen in the proximal component of the OFT cushions
• lack of tdTomato cNCCs in the proximal outflow cushion is less severe at E11.5; abundant cNCCs are found in the distal and intermediate outflow cushions, but not in proximal cushions, consistent with delayed migration
• moreover, number of Pax3Cre-tdTomato expressing cells that co-express SOX10 is markedly decreased and the linear migration pattern from the neural tube toward the heart is disrupted; most of tdTomato positive-expressing cells lacking SOX10 expression are located rather peripherally
• N-cadherin staining showed upregulation of N-cadherin expression in migratory NCCs at E8.5 and E9.5
• time-lapse image analysis of explanted cultured cNCCs showed a significant decrease in migration velocity relative to controls
|
|
• 12.7% of explanted cultured cardiac neural crest cells (cNCCs) make cell-cell contacts versus 8.5% of control cNCCs; strikingly, 81% of those contacts fail to separate within 2 h versus only 31.2% in control cNCCs, suggesting increased cell-cell adhesion
|
|
• at E9.5, fewer tdTomato-labeled cNCCs are detected in the developing outflow tract (OFT) relative to control embryos, suggesting a delay in cNCC migration
• at E10.5, a nearly complete absence of tdTomato cNCCs is seen in the proximal component of the OFT cushions
• lack of tdTomato cNCCs in the proximal outflow cushion is less severe at E11.5; abundant cNCCs are found in the distal and intermediate outflow cushions, but not in proximal cushions, consistent with delayed migration
• moreover, number of Pax3Cre-tdTomato expressing cells that co-express SOX10 is markedly decreased and the linear migration pattern from the neural tube toward the heart is disrupted; most of tdTomato positive-expressing cells lacking SOX10 expression are located rather peripherally
• N-cadherin staining showed upregulation of N-cadherin expression in migratory NCCs at E8.5 and E9.5
• time-lapse image analysis of explanted cultured cNCCs showed a significant decrease in migration velocity relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brain defects
|
|
• impaired morphogenesis of craniofacial structures
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced
|
|
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced
|
|
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die within 2 weeks of the 4th injection of tamoxifen (4 injections administered over an 8 day period)
|
|
• starting after 3 injections of tamoxifen in mice at 6 - 9 months of age
• becomes significant 1 week after the 4th injection of tamoxifen
|
|
• elevated astrocyte activation in the hippocampal region 1 week after the last tamoxifen injection
|
|
• 1 week after the last tamoxifen injection
|
|
• enhanced lipid peroxidation and impaired electron transport chain activity and ATP production in mitochondria 1 week after the last tamoxifen injection
|
|
• elevated astrocyte activation in the hippocampal region 1 week after the last tamoxifen injection
|
|
• in the hippocampal region 1 week after the last tamoxifen injection
|
|
• 1 week after the last tamoxifen injection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when given tamoxifen at E10.5, at P21 the anterior region (lobules I-V) is reduced and the central region (lobules VI-VII) is preferentially expanded.
|
|
• when tamoxifen is given at E10.5, at P21 lobule VIII extends more laterally than normal, as do lobules I-V but only on one side
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show rescue of the limb clasping phenotype and the twisting movements seen in Tor1atm1Wtd/Tor1atm3.1Wtd Tg(Dlx5a-cre)1Mekk/0 mice
|
| N |
• mice show prevention of striatal cholinergic interneuron degeneration that occurs in Tor1atm1Wtd/Tor1atm3.1Wtd Tg(Dlx5a-cre)1Mekk/0 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice do not exhibit lethality, growth defects, or abnormal twisting movements or stiff postures, and exhibit normal brain with no gliosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show almost complete rescue of the abnormal postural (squinty eyes and twisted hindpaws) and development phenotypes seen in Tor1atm2Wtd/Tor1atm3.1Wtd Tg(Nes-cre)1Kln/0 mice
|
| N |
• mice exhibit partial rescue of the postnatal growth retardation seen in Tor1atm2Wtd/Tor1atm3.1Wtd Tg(Nes-cre)1Kln/0 mice from P8 to P28 and are fully restored to normal weight by P56
|
| N |
• mice do not exhibit neurodegeneration or gliosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Gli2 expression, but not Gli3 de-repression, rescues intestinal phenotypes in Smotm2Amc/Smotm2Amc Nkx3-2tm1(cre)Wez/Nkx3-2+ embryos
| N |
• intestinal development is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the vascular network of the limbs is denser and more complex
• metacarpal centers are enriched for thicker vessels originating from the axial artery
• metacarpal centers are wider and split into a denser and more complex network of small capillaries in the interdigital areas
• however, formation of avascular areas is not affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• uterus defects observed in Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa Pgrtm2(cre)Lyd/Pgr+ mice are rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with tamoxifen after neurogenesis (at E10.5) exhibit normal motor pool formation
|
|
• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice
|
|
• at E12.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti, adductor longus and magnus, and posterior gracilis muscle motor neurons compared with control mice
• at E14.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti muscle motor neurons compared with control mice
• however, motor neurons in adductor longus and magnus and posterior gracilis muscles recover by E14.5
|
|
• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E14 and E17 embryos
• normal in E12 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• a cone-shaped tubercle structure is discernable unlike in urethral epithelium knock-out of beta-catenin
|
|
• mice exhibit failed cloaca septation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at birth
|
| N |
• vascularization and bone formation in the diaphysis are normal
|
|
• similar to in Ihhtm1Amc homozygotes, orthotopic osteoblast differentiation is impaired as determined by marker expression
|
|
• at E15.5 and E18.5, the proliferative zone is slightly larger than in Ihhtm1Amc homozygotes but smaller than in wild-type mice
|
|
• vascularization of the hypertrophic zone is improved compared to in Ihhtm1Amc homozygotes
|
|
• columnar organization of chondrocytes is partially restored compared to in Ihhtm1Amc homozygotes but is still disorganized compared to in wild-type mice
|
|
• at E18.5, mice fail to exhibit bone deposition in the perichondrium flanking the hypertrophic regions where the bone collar normally forms in the long bones of wild-type mice
|
|
• similar to in Ihhtm1Amc homozygotes, orthotopic osteoblast differentiation is impaired as determined by marker expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• ovariectomized mice show an absent decidual response in uteri indicating that the endometrium is unable to undergo decidualization
|
|
|
• abnormal morphology of uterine glands, including fluid-filled glands
|
|
|
• marker analysis indicates that uterine glands are more differentiated, with a higher proportion of glandular to luminal cells
|
|
|
• uterine glands are twice the size in cell number as controls
|
|
|
• mice show an increased presence of neutrophils in uteri
|
|
|
• ovariectomized mice show an absent decidual response in uteri indicating that the endometrium is unable to undergo decidualization
|
|
|
• mice show an increased presence of neutrophils in uteri
|
|
|
• adult females in which endometriosis is induced by autotransplantation of uterine tissue to the mesenteric membrane show an increase in size of ectopic lesions; lesions show decreased epithelial cell proliferation, luminal epithelial cells that appear cuboidal instead of columnar, and most of the lesion volume is comprised of a large, fluid-filled central lumen
|
|
|
• females bred with wild-type males contain numerous cystic uterine glands
|
|
|
• endometrial architecture is altered in bred females
|
|
|
• abnormal morphology of uterine glands, including fluid-filled glands
|
|
|
• marker analysis indicates that uterine glands are more differentiated, with a higher proportion of glandular to luminal cells
|
|
|
• uterine glands are twice the size in cell number as controls
|
|
|
• females bred with wild-type males show enlarged and translucent uterine horns
|
|
|
• females bred with wild-type males do not reproduce
• however, 3 week old females stimulated with gonadotrophins and mated with wild-type males exhibit a normal number of fertilized ova, normal progesterone and estradiol serum levels and normal uterine and ovarian estradiol levels, indicating normal ovarian and luteal function
|
|
|
• females bred with wild-type males contain numerous cystic uterine glands
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups fail to survive after birth
|
| N |
• normal myogenesis
• both fast and slow fibers with normal morphology
• functional and utrastructural integrity normal
|
|
• newborns with severely deformed ribs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 90% of pups are viable with a normal life span and normal musculature
|
|
• occasionally
|
|
• reduced costochondral and costosternal regions of ribs
• newborns with normal rib cages but occasional anomalies
• floating ribs occasionally misshapen
• occasional osseous knob-like protrusions
|
|
• occasional fusion of cartillagenous portions of ribs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups are immobile and die shortly after birth
|
|
• myogenesis appears normal at E12.5
• increasing apoptosis until all differentiating myofibers are either dead or dying at E18.5
|
|
• newborns lack differentiated myofibers
• basophilic clumps of cellular debris suggest skeletal muscle forms and then degenerates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• profound reduction in the number of labeled mitochondria in the dorsal striatum
|
|
• mitochondria are spherical and enlarged with disorganized cristae
|
|
• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
|
|
• profound reduction in the number of labeled mitochondria in the dorsal striatum
|
|
• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5
• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature
• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4
• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4
• vessel regression in the retina is increased in tamoxifen treated mice
|
|
• endothelial cell proliferation is reduced
|
|
• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5
• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature
• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4
• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4
• vessel regression in the retina is increased in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• inferior fusion defects resulting in notching of the inferior portion
|
|
• rare but consistent phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E18.5 in mice treated with tamoxifen at E12.5 or E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die 2 to 3 days following administration of tamoxifen for three consecutive days after weaning
|
|
• following administration of one dose of tamoxifen after weaning, mice exhibit areas of the duodenum that are devoid of crypt cells
• however, crypt cells recover by 9 months of age
|
|
• following administration of one dose of tamoxifen after weaning, mice exhibit areas of the jejunum that are devoid of crypt cells
• however, crypt cells recover by 9 months of age
|
|
• following administration of one dose of tamoxifen after weaning
• however, normal weight is recovered by 9 months of age
|
|
• following administration of one dose of tamoxifen after weaning, mice exhibit areas of the duodenum that are devoid of crypt cells
• however, crypt cells recover by 9 months of age
|
|
• following administration of one dose of tamoxifen after weaning, mice exhibit areas of the jejunum that are devoid of crypt cells
• however, crypt cells recover by 9 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lens from 2 day old mice exhibit cortical inhomogenicity
• lens fiber mass decreases with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E14.5, mice exhibit blood-filled cutaneous lymphatics unlike in wild-type mice
• neonates exhibit blood-filled mesenteric lymphatics unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• levels of cAMP are higher in cystic kidneys of the offspring of E17.5 pregnant females injected with tamoxifen
|
|
• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• when E17.5 pregnant females are injected intraperitoneally with tamoxifen to induce ubiquitous deletion of Ttc21b, the 6 week old offspring develop cystic kidney disease
• cysts seen in the offspring of E17.5 pregnant females injected with tamoxifen originate from proximal tubules, loops of Henle, and collecting ducts
• 5 week old mice injected intraperitoneally with tamoxifen do not develop kidney cysts after 3 months
• kidneys from offspring of E17.5 pregnant females grown in culture in the presence of 8-bromo-cAMP exhibit increased cystogenic potential and treatment of these cultures with Gant61, a small molecule GLI antagonist, or Sant2, a small molecule SMO antagonist, inhibitors reduces cystogenic potential
|
|
• elevation in ratio of percent kidney weight to body weight is seen in the offspring of E17.5 pregnant females injected with tamoxifen
|
|
• dilations of loops of Henle in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
|
|
• dilations of proximal tubules in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
|
|
• increase in BUN levels is seen in the offspring of E17.5 pregnant females injected with tamoxifen
|
|
• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
|
|
• when E17.5 pregnant females are injected intraperitoneally with tamoxifen to induce ubiquitous deletion of Ttc21b, the 6 week old offspring develop cystic kidney disease
• cysts seen in the offspring of E17.5 pregnant females injected with tamoxifen originate from proximal tubules, loops of Henle, and collecting ducts
• 5 week old mice injected intraperitoneally with tamoxifen do not develop kidney cysts after 3 months
• kidneys from offspring of E17.5 pregnant females grown in culture in the presence of 8-bromo-cAMP exhibit increased cystogenic potential and treatment of these cultures with Gant61, a small molecule GLI antagonist, or Sant2, a small molecule SMO antagonist, inhibitors reduces cystogenic potential
|
|
• elevation in ratio of percent kidney weight to body weight is seen in the offspring of E17.5 pregnant females injected with tamoxifen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cystic kidney disease | DOID:2975 | J:213263 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased apoptosis of cranial neural crest cells that is slight at E8.0, over 30-fold at E9.5 and 4-fold at E10.5
|
|
• considerable at E8.0, modest at E9.5, and 4-fold at E10.5
|
|
• reduced intensity of reporter expressing cells in the frontonasal prominence and pharyngeal arch 1 at E9.5 and throughout the facial processes at E10.5
• absence of obvious NCC streams entering the pharyngeal arches at E10.5
|
|
• decreased apoptosis of cranial neural crest cells that is slight at E8.0, over 30-fold at E9.5 and 4-fold at E10.5
|
|
• considerable at E8.0, modest at E9.5, and 4-fold at E10.5
|
|
• reduced intensity of reporter expressing cells in the frontonasal prominence and pharyngeal arch 1 at E9.5 and throughout the facial processes at E10.5
• absence of obvious NCC streams entering the pharyngeal arches at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 33% of mutants show fusion of ribs in the thoracic region
|
|
• neonates show vertebral malformations with a higher penetrance at the cervical level than at thoracic and lumber regions
|
|
• reduction in the number of thoracic vertebrae (12 instead of 13)
|
|
• absence of the tuberculum anterior on C6
|
|
• some mutants only have five lumbar vertebrae instead of six
|
|
• cervical regions show malformed neural arches
|
|
• neonates show vertebral fusions with a higher penetrance at the cervical level than at thoracic and lumber regions
• cervical vertebra 1 and associated anterior arch of the atlas are fused to the basioccipital bone
|
|
• neonates show the presence of a high number of homeotic transformations
• C2/C3 are anteriorly transformed
|
|
• cervical regions show anterior homeotic transformations
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered alpelisib, a PIK3CA inhibitor, daily starting 48 hours after cre induction (preventative alpelisib) exhibit a normal appearance during the 22 weeks of treatment and a body weight increase similar to that of controls
• mice administered alpelisib 2 weeks after cre induction when global muscle hypertrophy is already prominent for 20 additional weeks (therapeutic alpelisib), show a rapid body weight decrease
• 6-week-old mice treated with tamoxifen for 5 days show progressive weight gain starting at 3 weeks after treatment which is not seen in wild-type mice and around 11 weeks after induction in males and 24 weeks in females, body weight becomes lower than in wild-type mice
|
|
• mitochondrial mass is reduced in striated muscle cells of tamoxifen-treated mice
|
|
• mice show skeletal muscle hypertrophy at 15 weeks after tamoxifen, with hypertrophic striated cells
• mice administered alpelisib, a PIK3CA inhibitor, daily starting 48 hours after cre induction (preventative alpelisib) exhibit no skeletal muscle overgrowth 8 weeks after alpelisib initiation indicating that alpelisib prevents skeletal muscle overgrowth
• mice treated with therapeutic alpelisib show a reduction in muscular volume and striated muscle is conserved indicating that alpelisib reverses skeletal muscle overgrowth
|
|
• striated muscle cells from tamoxifen-treated mice show an alteration in the mitochondrial transmembrane potential
|
|
• tamoxifen-treated mice show higher fluoro-D-glucose muscular uptake
|
|
• tamoxifen-treated mice show reduced fat content
|
|
• tamoxifen-treated mice show a gain in muscle strength
|
|
• tamoxifen-treated mice show higher fluoro-D-glucose muscular uptake
|
|
• striated muscle cells from tamoxifen-treated mice show an alteration in the mitochondrial transmembrane potential
|
|
• plasma metabolites metabolomics analysis of tamoxifen-treated mice show metabolic changes with increases in acetyl-aspartate, acetyl-glutamine, acetyl-lysine, aminoadipate, ATP, camosine, citrate, creatinine, cytidine, decanoic acid, dodecanoyl-carnitine, dodecanoic acid/lauric acid, docosahexaenoic acid, hexanoic acid, hexanoyl-carnitine, linoleic acid, linolenic acid, methyl-lysine, myristic acid, myristoyl-carnitine, octanoyl-carnitine, oleic acid, O-phosphoethanolamine, palmitic acid, palmitoyl-carnitine, palmitoleic acid, phosphocreatine, riboflavin, S-adenosyl-L-homocysteine, and taurine, and decreases in glutamate, glucose, L-alanine, lysine, methionine, ornithine, threonine, tryptophan, and tyrosine
• alpelisib treatment results in partial correction of the different metabolic anomalies
|
|
• tamoxifen-treated mice are hypoglycemic
• mice treated with preventative alpelisib show normal 12-h fasted glycemia
• mice treated with therapeutic alpelisib show increased blood glucose levels
|
|
• mice treated with therapeutic alpelisib show increased insulin levels
• however, mice show conserved insulin secretion in the oral glucose tolerance test
• mice treated with preventative alpelisib show corrected circulating insulin levels
• tamoxifen-treated mice exhibit low insulin levels
|
|
• tamoxifen-treated mice show low IGF1 levels
• mice treated with preventative alpelisib show corrected IGF1 levels
• mice treated with therapeutic alpelisib show increased circulating IGF1 levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at birth
|
| N |
• unlike in Ihhtm1Amc Gli3Xt-J homozygotes the marrow cavity and hypertrophic chondrocyte are normal
|
|
• the growth region cartilage is longer than in wild-type mice
• the columnar zone contains areas of disorganization unlike in wild-type mice
• however, orthotopic bone collar formation is normal unlike in Ihhtm1Amc homozygotes
|
|
• while larger than Ihhtm1Amc homozygotes at E18.5, mice are smaller than wild-type mice
|
|
• while larger than in Ihhtm1Amc homozygotes at E18.5, limbs are shorter than in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice exhibit blood-filled Peyer patches unlike in wild-type mice
|
|
• mice exhibit blood-filled mesenteric and intestinal lymphatic vessels unlike wild-type mice
|
|
• platelets from neonates without vascular phenotypes exhibit intermediate levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells
|
|
• platelets from neonates without vascular phenotypes exhibit intermediate levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells
|
|
• some mice exhibit blood-filled Peyer patches unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mitochondria abnormalities in Tfamtm1Lrsn/Tfamtm1Lrsn Slc6a3tm1(cre)Lrsn/Slc6a3+ Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ neurons
|
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
|
|
• smaller mitochondrial and the largest aggregates in a rare number of neurons exhibit reduced import competence compared with mitochondria in control cells
|
|
• impaired from 20 weeks of age
|
|
• from 20 weeks of age
|
|
• rigidity from 20 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal regulatory T cell differentiation and homeostasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal mitochondrial network in Afg3l2tm1Arte/Afg3l2tm1Arte Tg(Pcp2-cre)2Mpin/0 Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ mice
|
• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
|
|
• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
|
|
• Purkinje cell electrophysiological properties are normal at 4 to 5 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• live embryos at E18.5 but no live progeny
|
|
• severe craniofacial deformation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• live to 3 months
|
|
• mice are very small
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fully penetrant tumorigenesis when tamoxifen is injected after 3 weeks of age
• tumors in deep mesenchymal tissues of the limbs and trunk
• most tumors form adjacent to bone but some are totally in muscle
• all tumors with "clear cell" morphology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice display mild shortening of the palate
|
| N |
• unlike Pax3tm1(cre)Joe homozygotes, hind limb morphology is normal
|
| N |
• unlike Pax3tm1(cre)Joe homozygotes, diaphragm morphology is normal
|
|
• mice display mild shortening of the palate
|
|
• mice display mild shortening of the palate
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• noncompacted trabeculae in ventricular myocardium in E15.5 embryos
|
|
• in E15.5 embryos
• reduced compact-to-trabecular myocardium ratio in E15.5 embryos
|
|
• in E15.5 embryos
• reduced compact-to-trabecular myocardium ratio in E15.5 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal hearts in E15.5 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• regulatory T cells exhibit normal suppressive functions and stability
|
|
• severe
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop intracranial tumors 10-14 weeks after tamoxifen treatment at 2 weeks of age
• tumors are located either within the brain parenchyma or it the periosteum along the inner table of the cranium
• however, no tumors are seen in the outer table periosteum or the limbs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are stillborn
|
| N |
• placenta organization is grossly normal
|
|
• exaggerated curvature
• however, supplementation with choline improves caudal body axis size
|
|
• visible as early as E11.5
• evident at E16.5 without full penetrance
• open spina bifida in 9 of 13 pups
• treatment with oral nicotine increases spina bifida incidence and severity
• however, supplementation with folic acid and choline reduces frequency of occurrence
|
|
• rare and restricted to the mandible
|
|
• enlarged teeth at E16.5
|
|
• enlarged teeth at E16.5
|
|
• with peritoneal membrane enclosing the extruded liver and intestine at E16.5
|
|
• evident at E16.5 without full penetrance
• protrusion of abdominal organs (liver and intestines) suggestive of an omphalocele
|
|
• at E16.5
|
|
• abnormal proportioned limbs in stillborn mice
|
|
• reminiscent of Grhl3ct
• reverted tail tip
• tail defects are not improved by folic acid supplementation
• however, supplementation with choline improves tail bud defects
|
|
• visible as early as E11.5
• evident at E16.5 without full penetrance
• open spina bifida in 9 of 13 pups
• treatment with oral nicotine increases spina bifida incidence and severity
• however, supplementation with folic acid and choline reduces frequency of occurrence
|
|
• extruded dorsal root ganglia at E16.5
|
|
• absence or disorganized at E16.5
|
|
• in stillborn mice
|
|
• at E16.5
|
|
• at E16.5
|
|
• at E16.5
|
|
• absence or disorganized at E16.5
|
|
• enlarged teeth at E16.5
|
|
• abnormal proportioned limbs in stillborn mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in tamoxifen-treated mice following CTX-induced muscle injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• both genes are expressed in ovaria, but ovulation, fertilization, preimplantation embryo development and hormone production are normal in conditional gain-of-function females
|
|
|
• persistent apicobasal polarity in the luminal epithelium with increased cell heights and retention of glycosylated microvilli on the apical surface
|
|
|
• abnormal primary decidual zone (PDZ) development at 6 dpc
• PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc
|
|
|
• uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc
• unattached blastocysts were recovered from uteri at 5 dpc
• defects in crypt formation
• some blastocysts situated within the primary lumen
|
|
|
• inappropriate mesometrial-antimesometrial (M-AM) orientation of implantation sites at 5, 6 and 8 dpc: closer to M pole instead of at AM pole
• ratio of M-AM axis length to anterior-posterior (A-P) axis length is reduced by ~25% resulting in a more spherical morphology at 8 dpc
|
|
|
• uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc
• different sizes of implantation sites at 8 dpc
|
|
|
• implantation sites were often irregularly spaced at 5 and 8 dpc
|
|
|
• two embryos closely apposed within one implantation site
|
|
|
• plug-positive females are either sterile or produce a small litter
• high resorption rates
|
|
|
• in the few fertile mice
|
|
|
• clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc
|
|
|
• increasing numbers of resorption sites on 10 and 12 dpc
• absent or substantially smaller embryos in many implantation sites from 10 dpc
|
|
|
• in surviving implantation sites at 12 dpc
• disrupted placental development from 10 dpc
|
|
|
• abnormal primary decidual zone (PDZ) development at 6 dpc
• PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc
|
|
|
• Gcm1-positive syncytiotrophoblasts in the labyrinth failed to elongate, suggesting disrupted secondary branching morphogenesis of placental villi at 12 dpc
|
|
|
• clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 42% reduction in muscle connective tissue fibroblasts after 5 doses of tamoxifen
|
|
• ablation of fibroblasts leads to 51% reduction in muscle satellite cells 5 days post injury
|
|
• at 3 days post injury fibroblasts are reduced 19% but myofiber regeneration is increased 5 fold
• leads to depletion of satellite cell pool and reduction in regenerating myofibers at 5 days
• tibialis anterior muscle is regenerated at 28 days after injury but somewhat smaller in cross-sectional area
• satellite cell numbers have recovered after 28 days
• smaller diameter of regenerated myofibers
• muscle size differences are no longer significant at 56 days after injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• mice fail to elicit a differential response in a glucose tolerance test
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shortened head
|
|
• mice are smaller at 6 months of age, with average mass reduced by 30%
• however, mice maintained in the presence of doxycycline exhibit normal skeletal phenotypes
|
|
• shortening of the trunk in 6 and 10 week old mice
|
|
• reduction in length/width ratio of the skull
|
|
• the extracellular content of collagen II is reduced in growth plates
• the collagenous matrix in growth plates lacks structural continuity and the longitudinal septa are irregularly thickened
• polarity of proliferating chondrocytes and periarticular chondrocytes in the growth plates is not clearly defined
• the parallel organization of primary cilia in chondrocytes of the growth plates of newborns is not clearly established and the uniform pattern of primary cilia alignment in growth plates of 10 week old mice is not apparent
|
|
• 10 week old mice show irregular distribution of collagen X-rich matrix in the hypertrophic zones
|
|
• tibial growth plates show disorganized columnar chondrocytes whose continuity of the typical palisade-like arrangement is often interrupted by extended areas in which chondrocytes are absent
|
|
• vertebrae are shorter and wider
|
|
• diameter of collagen fibrils in the growth plates is small
|
|
• polarity of proliferating chondrocytes and periarticular chondrocytes in the growth plates is not clearly defined
|
|
• percent of chondrocytes undergoing division is lower in newborn and 10-week old mutants than in controls, indicating decreased proliferation
• an increase in BiP content indicates that chondrocytes are undergoing endoplasmic reticulum stress
|
|
• aberrant organization of primary cilia in chondrocytes of growth plates
• length of cilia present in growth plate chondrocytes is reduced
|
|
• reduction in length/width ratio of the skull
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| spondyloepiphyseal dysplasia congenita | DOID:14789 |
OMIM:183900 |
J:216945 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• starting in E9.5 embryos, worsening with age
|
|
• starting in E9.5 embryos, worsening with age
|
| N |
• normal outflow tract septation in E12 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median lip notches in some E14-E15 embryos
|
|
• in some E14-E15 embryos
|
|
• in some E14-E15 embryos
|
|
• in some E14-E15 embryos
|
|
• median lip notches in some E14-E15 embryos
|
|
• in some E14-E15 embryos
|
|
• in some E14-E15 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in the spleen of tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• tamoxifen-treated mice exhibit disturbed cell distribution with pronounced dysplasia and disrupted maturation in the erythroid, megakaryocytic and granulocytic lineages compared with control mice
• bone marrow from tamoxifen-treated mice exhibit reduced formation of colony forming units compared with control mice
• however, tamoxifen-treated mice exhibit normal numbers of hematopoietic stem cells
|
|
|
• decreased granulocyte-macrophage progenitors and macrophage colony numbers from bone marrow of tamoxifen-treated mice
|
|
|
• abnormal nuclear lobation and atypical mitosis in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• dysplastic granulocytes with nuclear hyposegmentation in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in the spleen of tamoxifen-treated mice
|
|
|
• relative in tamoxifen-treated mice
|
|
|
• impaired migration in hematopoietic stem and progenitor cells of tamoxifen-treated mice
|
|
|
• increased chromosomal double-strand breaks and numerical and structural chromosomal aberrations 2 weeks after tamoxifen-treatment
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• anemic appearance of the bones in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• dysplastic granulocytes with nuclear hyposegmentation in tamoxifen-treated mice
|
|
|
• in the spleen of tamoxifen-treated mice
|
|
|
• relative in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• tamoxifen-treated mice exhibit normal blood counts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly smaller than control littermates
|
|
• significantly smaller than control littermates
|
|
• reduction in liver Igf1 mRNA levels indicates a reduction in circulating growth hormone levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells either do not leave thymus or fail to migrate into the blood and to the peripheral lymphoid organs
|
|
• T cells either do not leave thymus or fail to migrate into the blood and to the peripheral lymphoid organs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in one mouse
|
|
• in one mouse
|
|
• in one mouse
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die within a few hours of birth
|
|
• cutaneous branch of the ventral ramus is absent in E14.5 embryos
• innervation of the distal limbs at E14.5 confirmed a nearly complete loss of fine cutaneous sensory fibers with only a single sensory branch innervating one side of digits 1, 2 and 5 in both the forelimb and hindlimb
|
|
• there is an increased rate of apoptosis within the trigeminal ganglia of E11.5 and E12.5 embryos
|
|
• the dorsal root ganglion (DRG) of E12.5 embryos do not express Isl1 protein
• TrkA+ neurons are lower in number starting at E12.5 and by E14.5 are less than one-third of what is found in controls
• TrkB+ neurons are also lower in number starting at E12.5 and are markedly reduced at E14.5 and birth
• TrkC+ neurons do not appear until E12.5, a delay of two days compared to controls
|
|
• the DRG of E14.5 embryos is markedly smaller than controls with a smaller number neurons found within the ganglion
• an increased rate of apoptosis is noted in the E12.5 DRG
|
|
• mice have a reduced response to a mild noxious stimulus that was applied to the skin of the trunk or limbs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike in mice lacking Fgf8 over-expression, mice develop normal humeri with deltoid tuberosity and the radius is evident
|
|
• autopod rudiments
|
|
• the ulna is longer and thicker
|
|
• near normal pelvic girdles and femurs with one or two ectopic cartilages
|
|
• the ulna is longer and thicker
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5
• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature
• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4
• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4
• vessel regression in the retina is increased in tamoxifen treated mice
|
|
• endothelial cell proliferation is reduced
|
|
• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5
• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature
• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4
• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4
• vessel regression in the retina is increased in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die 5 weeks after birth
|
|
• after P25
|
|
• mice lack coat pigment in the trunk
|
|
• enteric neural crest cells fail to reach the anus
|
|
• mice lack coat pigment in the trunk
|
|
• enteric neural crest cells fail to reach the anus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced +GFP craniofacial neural crest cells in nasal prominences and pharyngeal arches due to increased apoptosis between E9.5 and E10.5
|
|
• reduced +GFP craniofacial neural crest cells in nasal prominences and pharyngeal arches due to increased apoptosis between E9.5 and E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E14.5, cells expressing lacZ are found across the dorsal and posterior borders of the thalamus expanding into the epithalamus and pretectum
• ectopic lacZ expressing cells from the thalamus are mainly found in the lateral habenular nuclei and anterior part of the pretectum at E18.5
|
|
• at E10.5 the thalamus is smaller in the mediolateral dimension and larger in the ventrodorsal dimension
• thalamus morphology is severely disrupted after E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment mild defects in thalamus morphology are seen in some mutants with high levels of recombination but for the most part defects in establishment of dorsal and posterior thalamic boundaries seen in null mice are not seen
• this result and chimera experiments suggest that the function of Gbx2 is cell nonautonomous
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show a moderate incidence of epithelial hyperplasia in the anterior prostate
|
|
|
• one mouse shows a prostatic intraepithelial neoplasia (mPIN) in the dorsolateral prostate
|
|
|
• one mouse shows a prostatic intraepithelial neoplasia (mPIN) in the dorsolateral prostate
|
|
|
• mice show a moderate incidence of epithelial hyperplasia in the anterior prostate
|
|
|
• one mouse shows a prostatic intraepithelial neoplasia (mPIN) in the dorsolateral prostate
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline (Dox)-treated mice show a gradual reduction in the volume of adipose tissue
• when mice are taken off the Dox-containing diet, the fat tissue volume increases
|
|
• increase in serum free fatty acids in the fed state after 72 hours of induction with Dox
• however, Dox-treated mice maintain the same rate of fatty acid and cholesterol synthesis as controls in a biochemical assay for de novo lipid synthesis
|
|
• mice fed a doxycycline (Dox)-containing diet show a higher respiratory exchange ratio than wild-type mice during the dark phase
|
|
• mice exhibit a reduction in hepatic glucose release when exposed to Dox for 48 hours
• metabolic cage studies indicate higher glucose utilization in Dox-treated mice
|
|
• a 6-hour fast causes severe hypoglycemia within 48 hours after induction with Dox
|
|
• serum glucose levels start to decrease by 72 hours after induction with Dox under fed conditions
• administration of a PPAR-alpha agonist exacerbates the hypoglycemia in Dox-treated mice
|
|
• fed insulin levels start to decrease upon induction with Dox and are significantly lower by 72 hours of induction
• 96 hours after Dox-induction, fasted insulin levels are lower
|
|
• hepatic glycogen is severely depleted after 48 hours of induction with Dox
|
|
• livers of Dox-treated mice show a faster response to insulin exposure and isolated hepatocytes induced with Dox show an enhanced insulin response indicating hepatic insulin sensitivity
|
|
• hepatic triglyceride content is increased in Dox-treated mice
• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure
|
|
• the fasting effects of adipocyte lipolysis on hepatic triglyceride content are exacerbated in Dox-treated mice compared to wild-type mice
|
|
• liver mass is increased 1.7-fold within 48 hours of induction with Dox
• Dox-treated mice show reduced dry mass content per wet liver
• increase in total liver protein in Dox-treated mice
|
|
• hepatic glycogen is severely depleted after 48 hours of induction with Dox
|
|
• hepatic triglyceride content is increased in Dox-treated mice
• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure
|
|
• Dox-treated mice show an increase in hepatic lipid levels
• when mice are taken off the Dox-containing diet, the liver steatosis decreases rapidly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice exhibit disorganized Bergmann glial scaffolds with loose and wavy glial fibers
• endfeet of Bergmann glial fibers in tamoxifen-treated mice fail to maintain adhesion to the basement membrane unlike in control mice
|
|
• tamoxifen-treated mice exhibit increased number of granule cell precursors in the external granule layer
|
|
• granule cells in tamoxifen-treated mice are trapped in the external granule layer unlike in control mice
|
|
• at P19, tamoxifen-treated mice exhibit severely compromised ingression of several fissures compared with control mice
|
|
• tamoxifen-treated mice exhibit the same lobule defects as in Ric8tm1Zhua/Ric8tm1Zhua Tg(GFAP-cre)25Mes mice
• however, fissural basement membrane is normal
|
|
• tamoxifen-treated mice exhibit the same lobule defects as in Ric8tm1Zhua/Ric8tm1Zhua Tg(GFAP-cre)25Mes mice
|
|
• tamoxifen-treated mice exhibit disorganized Bergmann glial scaffolds with loose and wavy glial fibers
• endfeet of Bergmann glial fibers in tamoxifen-treated mice fail to maintain adhesion to the basement membrane unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• infrequently, mice exhibit occurrence of invasive pancreatic ductal adenocarcinoma after long latency (35-70 weeks) following doxycline treatment
|
|
• mice develop PanIN lesions within 2 weeks of doxycycline induction
|
|
• mice develop acinar-to-ductal metaplasia within 2 weeks of doxycycline induction
|
|
• infrequently, mice exhibit occurrence of invasive pancreatic ductal adenocarcinoma after long latency (35-70 weeks) following doxycline treatment
|
|
• mice develop PanIN lesions within 2 weeks of doxycycline induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice exhibit a increase metaphyseal microvascular density compared to in wild-type mice
|
|
• following doxycycline treatment for the first 2 weeks of life, growing long bones are abnormal in shape and morphology with abundant stromal cells and blood vessels surrounding numerous trabeculae unlike in wild-type mice
• adult mice treated with doxycycline for 14 days exhibit lamellar cortical bone is replaced with trabecular-like porous bone structure with abundant intercalating mesenchymal tissue components and osteoclast-rich remodelling units unlike in wild-type mice
|
|
• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice
• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment
|
|
• in doxycycline-treated mice, bone marrow blood vessels exhibit hemangioma-like morphology and are filled with erythrocytes unlike in wild-type mice
• in doxycycline-treated mice, hematopoietic bone marrow is replaced with new bone, marrow fibrosis, and aberrant blood vessels displaying paucity of myeloid cells unlike in wild-type mice
|
|
• doxycycline-treated mice exhibit bone marrow fibrosis unlike in wild-type mice
|
|
• adult mice treated with doxycycline for 14 days exhibit disrupted bone architecture with abundant peritrabecular mesenchymal stromal cells in the metaphyseal and epiphyseal regions compared with wild-type mice
|
|
• adult mice treated with doxycycline for 14 days exhibit a 70% increase in trabecular density compared with wild-type mice
|
|
• adult mice treated with doxycycline for 14 days exhibit increased metaphyseal trabecular bone mass compared with wild-type mice
|
|
• at E16.5, doxycycline-treated mice exhibit increased cell proliferation in the perichondrium/periosteum and throughout the primary ossification center compared with wild-type mice
• adult mice treated with doxycycline exhibit increased proliferation of the mesenchymal cells in the metaphysis, epiphysis, and periosteum compared with wild-type mice
|
|
• in doxycycline-treated mice as determined by marker expression
|
|
• doxycycline-treated mice exhibit a increase in growth plate mineralization compared to in wild-type mice
|
|
• doxycycline-treated mice exhibit a mild decrease in growth plate thickness compared to in wild-type mice
|
|
• increased following doxycycline treatment
|
|
• doxycycline-treated mice exhibit reduced bone resorption in the diaphyses and metaphysis compared with wild-type mice
• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment
|
|
• doxycycline-treated mice exhibit an increase in CFU-Cs (colony-forming units in culture) in the peripheral blood and spleen compared with wild-type mice
• however, bone marrow CFUs of doxycycline-treated mice are normal
|
|
• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis
|
|
• as indicated by enlarged spleen size in 25% of doxycycline-treated mice
|
|
• in the spleen of doxycycline-treated mice
|
|
• the number of megakarypcyte and progenitor cells in the spleens of doxycycline-treated mice is increased compared to in wild-type mice
|
|
• small after 2 weeks of doxycycline treatment
|
|
• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice
• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment
|
|
• in the peripheral blood of doxycycline-treated mice
|
|
• following doxycycline treatment, bone vasculogenesis is increased compared to in wild-type mice
• in doxycycline treated mice, bone marrow blood vessels exhibit hemangioma-like morphology and are filled with erythrocytes unlike in wild-type mice
|
|
• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis
|
|
• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice
• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment
|
|
• in doxycycline-treated mice as determined by marker expression
|
|
• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit severe long bone kyphosis unlike in Gt(ROSA)26Sortm1Jhai Tg(Col2a1-cre)1Bhr mice
|
|
• bone shafts in mice are wider than in wild-type mice
|
|
• mice exhibit hypervascularization in the expanded perichondrial/periosteal region and inside the bone shaft compared with wild-type mice
|
|
• mice exhibit an increase in mineralized bone formed compared with wild-type mice that is not as severe as in Gt(ROSA)26Sortm1Jhai Tg(Col2a1-cre)1Bhr mice
|
|
• mesenchymal hyperproliferation in mice is reduced compared to in Gt(ROSA)26Sortm1Jhai Tg(Col2a1-cre)1Bhr mice
|
|
• mice exhibit hypervascularization in the expanded perichondrial/periosteal region and inside the bone shaft compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at birth
|
|
• long bones are abnormal and bent (kyphosis) compared to in wild-type mice
• however, skeletal patterning and growth is normal
|
|
• at E16.5, limb diaphyses are short and thick compared to in wild-type mice
• at E16.5, primary ossification centers are malformed compared to in wild-type mice
• at E16.5, ossification centers are laterally expanded with excessive, disorganized bone compared to in wild-type mice
|
|
• at E16.5, rib diaphyses are short and thick compared to in wild-type mice
|
|
• at E16.5, limb and rib diaphyses are short and thick compared to in wild-type mice
• bone lack a proper cortex and abnormally oriented trabecular-like structures extend inside the bone, obliterating the developing marrow cavity unlike in wild-type mice
• mice exhibit increased blood vessels in the bone compared with wild-type mice
|
|
• abnormally oriented trabecular-like structures extend inside the bone, obliterating the developing marrow cavity unlike in wild-type mice
|
|
• at E16.5, primary ossification centers are malformed compared to in wild-type mice
• at E16.5, ossification centers are laterally expanded with excessive, disorganized bone compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit fragmented mitochondria, unlike in control mice
|
|
• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit swollen mitochondria, unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice show progressive and rapid loss of targeted (mt-YFP+) oligodendrocytes in the corpus callosum after 6 weeks of age, with only a few targeted cells remaining at 28 weeks
• at 10 weeks, the number of total APC+ cells is significantly decreased both in the corpus callosum and in the spinal cord
• at 10 weeks, the % of mt-YFP+ cells in the corpus callosum that are also APC+ is significantly reduced, while the % of APC- Olig2- targeted cells is significantly increased
• surprisingly, the number of mature oligodendrocytes and the size of APC+ cells is increased at 28 weeks of age; enlarged APC+ cells do not co-localize with mt-YFP+ cells but are in fact intensively positive for Olig2 staining
|
|
• at 10 weeks of age, non-myelinating Schwann cells in the subcutaneous nerve plexus show a significant decrease of mt-YFP signal
• at 10 weeks of age, tamoxifen-treated mice show clear signs of Schwann cell pathology affecting preferentially small calibre unmyelinated fibers; several Remak bundles appear affected with individual unmyelinated axons touching each other and showing initial signs of axonal degeneration; inner tongue swellings are also observed in myelinated axons
|
|
• tamoxifen-treated mice show death of mature oligodendrocytes followed by compensatory repopulation by untargeted oligodendrocytes
• at 8 weeks of age, several oligodendrocytes undergo dark cell death, a caspase-independent form of death characterized by strong cytoplasmic condensation, chromatin clumping, ruffling of the cell membrane, but no blebbing of the nucleus or plasma membrane
• only a few TUNEL+ apoptotic cells are noted in the corpus callosum at 7 weeks of age
|
|
• at 10 weeks of age, tamoxifen-treated mice show a strong reduction of mt-YFP+ melanoblasts in the outer root sheath of the hair follicle
• at 28 weeks of age, pigmented hair follicles and c-KIT+ melanoblasts are significantly reduced in dorsal skin, suggesting that premature hair greying is caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells
|
|
• at 10 weeks of age, tamoxifen-treated mice show a reduction of mt-YFP signal within the sciatic nerve
|
|
• at 28 weeks of age, non-myelinated large caliber axons and multivesicular disintegration of adaxonal myelin lamellae are observed in the sciatic nerve
|
|
• tamoxifen-treated mice show progressive and rapid loss of targeted (mt-YFP+) oligodendrocytes in the corpus callosum after 6 weeks of age, with only a few targeted cells remaining at 28 weeks
• at 10 weeks, the number of total APC+ cells is significantly decreased both in the corpus callosum and in the spinal cord
• at 10 weeks, the % of mt-YFP+ cells in the corpus callosum that are also APC+ is significantly reduced, while the % of APC- Olig2- targeted cells is significantly increased
• surprisingly, the number of mature oligodendrocytes and the size of APC+ cells is increased at 28 weeks of age; enlarged APC+ cells do not co-localize with mt-YFP+ cells but are in fact intensively positive for Olig2 staining
|
|
• at 10 weeks of age, non-myelinating Schwann cells in the subcutaneous nerve plexus show a significant decrease of mt-YFP signal
• at 10 weeks of age, tamoxifen-treated mice show clear signs of Schwann cell pathology affecting preferentially small calibre unmyelinated fibers; several Remak bundles appear affected with individual unmyelinated axons touching each other and showing initial signs of axonal degeneration; inner tongue swellings are also observed in myelinated axons
|
|
• at 6 weeks of age, oligodendrocytes of tamoxifen-treated mice exhibit swollen mitochondria
|
|
• tamoxifen-treated mice show death of mature oligodendrocytes followed by compensatory repopulation by untargeted oligodendrocytes
• at 8 weeks of age, several oligodendrocytes undergo dark cell death, a caspase-independent form of death characterized by strong cytoplasmic condensation, chromatin clumping, ruffling of the cell membrane, but no blebbing of the nucleus or plasma membrane
• only a few TUNEL+ apoptotic cells are noted in the corpus callosum at 7 weeks of age
|
|
• at 8 but not at 6 weeks of age, oligodendrocytes of tamoxifen-treated mice exhibit loss of COX1 staining, indicating impaired mitochondrial function
• cytochrome c is undetectable in several swollen mitochondria in oligodendrocytes at 8 weeks of age
|
|
• at 10 weeks of age, tamoxifen-treated mice show a strong reduction of mt-YFP+ melanoblasts in the outer root sheath of the hair follicle
• at 28 weeks of age, pigmented hair follicles and c-KIT+ melanoblasts are significantly reduced in dorsal skin, suggesting that premature hair greying is caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells
|
|
• at 28 weeks of age, tamoxifen-treated mice show reduced fat deposited in the dermis
• however, general skin structure is normal
|
|
• at 28 weeks of age, c-KIT+ melanocytes are significantly reduced in dorsal skin
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• beta-cells show elevated mitochondrial membrane potential (hyperpolarization) under basal conditions that collapses upon elevated glucose exposure; this loss of mitochondrial membrane potential indicates an inability to maintain the mitochondrial electron gradient under high glucose
• acute treatment with rapamycin mitigates the hyperpolarization seen in beta-cells and the loss of mitochondrial membrane potential with high glucose exposure is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at E9.5 and E10.5, normal patterns of GFP-labeled cranial neural crest cells (CNCCs) are seen in the frontonasal and periocular regions as well as in the branchial arches
• at E10.5, the contribution of GFP-labeled CNCCs in the nasal, maxillary, and mandibular processes is similar to that in control embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice challenged with sheep red blood cell (sRBC) immunization show an increase in T follicular cells
|
|
• tamoxifen-treated mice challenged with sRBC immunization show expanded germinal center (increased GL7/B220+ B cells)
|
|
• mice treated with tamoxifen in adulthood and challenged with sRBC immunization show altered adaptive response after immunization, with more T follicular (Tfol) cells, expanded germinal centers (GCs; increased GL7/B220+ B cells) and higher titers of serum anti-sRBC IgG
|
|
• tamoxifen-treated mice challenged with sRBC immunization show higher titers of serum anti-sRBC IgG
|
|
• tamoxifen-treated mice challenged with sheep red blood cell (sRBC) immunization show an increase in T follicular cells
|
|
• tamoxifen-treated mice challenged with sRBC immunization show expanded germinal center (increased GL7/B220+ B cells)
|
|
• tamoxifen-treated mice challenged with sRBC immunization show higher titers of serum anti-sRBC IgG
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• areas of nasal bones is reduced by about 20% at P0
|
|
• areas of nasal bones is reduced by about 20% at P0
|
|
• areas of nasal bones is reduced by about 20% at P0
|
|
• areas of nasal bones is reduced by about 20% at P0
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• in a glucose tolerance test, tamoxifen-treated mice show no differences in basal blood glucose or after an i.p. glucose bolus compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 8 and 18 weeks after doxycycline (dox) treatment to induce Kras2 expression due to pancreatic ductal adenocarinoma
|
|
• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion
• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant
|
|
• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma
|
|
• adult mice treated with dox for 5 weeks prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis exhibit a small, translucent remnant of pancreatic tissue, without fibrosis or PanIN lesions
• when dox is removed after pancreatitis induction, mice show show normal acini interspersed with dilated ducts and acinar-ductal metaplasia, fibrosis and occasional lipomatosis, but with minimal inflammatory infiltrate, and reduced proliferation
|
|
• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion
• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant
|
|
• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:184378 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 13.6% of mice develop prostatic adenocarcinoma from 8-21 months of age
• tumors are poorly circumscribed and unencapsulated, comprised of haphazard acini and lobules of pleomorphic cells
|
|
|
• mice develop atypical proliferative lesions indicating prostatic intraepithelial neoplasia (mPIN) as early as 8 weeks of age
• 40.9% of mice exhibit mPIN lesions
• mPIN lesions are mainly cribriform structures with occasional stratification of cells, papilliferous structures and tufts of cells
• atypical epithelial cells that are irregular, larger than adjacent normal cells, and lacking normal polarity are seen in all prostatic lobes, including anterior, dorsal and ventral prostate
• foci of atypical cells partially fill the lumen of the ducts
• mice exhibit intraluminal glands forming within the original glands in the dysplastic lesions
|
|
|
• mice develop atypical proliferative lesions indicating prostatic intraepithelial neoplasia (mPIN) as early as 8 weeks of age
• 40.9% of mice exhibit mPIN lesions
• mPIN lesions are mainly cribriform structures with occasional stratification of cells, papilliferous structures and tufts of cells
• atypical epithelial cells that are irregular, larger than adjacent normal cells, and lacking normal polarity are seen in all prostatic lobes, including anterior, dorsal and ventral prostate
• foci of atypical cells partially fill the lumen of the ducts
• mice exhibit intraluminal glands forming within the original glands in the dysplastic lesions
|
|
|
• malignancy, with vascular invasion by neoplastic cells or local invasion of the tumor beyond the basement membrane into surrounding stromal tissues is seen in some mice
|
|
|
• 13.6% of mice develop prostatic adenocarcinoma from 8-21 months of age
• tumors are poorly circumscribed and unencapsulated, comprised of haphazard acini and lobules of pleomorphic cells
|
|
|
• 13.6% of mice develop prostatic adenocarcinoma from 8-21 months of age
• tumors are poorly circumscribed and unencapsulated, comprised of haphazard acini and lobules of pleomorphic cells
|
|
|
• mice develop atypical proliferative lesions indicating prostatic intraepithelial neoplasia (mPIN) as early as 8 weeks of age
• 40.9% of mice exhibit mPIN lesions
• mPIN lesions are mainly cribriform structures with occasional stratification of cells, papilliferous structures and tufts of cells
• atypical epithelial cells that are irregular, larger than adjacent normal cells, and lacking normal polarity are seen in all prostatic lobes, including anterior, dorsal and ventral prostate
• foci of atypical cells partially fill the lumen of the ducts
• mice exhibit intraluminal glands forming within the original glands in the dysplastic lesions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate adenocarcinoma | DOID:2526 | J:234601 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1 of 2 mice treated with doxycycline (dox) at 4-6 weeks of age show frank adenocarcinoma by 23 weeks on dox
• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction
|
|
• mice treated with doxycycline (dox) at 4-6 weeks of age to induce Kras2 expression begin to show low-grade pancreatic intraepithelial neoplasia (PanIN) beginning at 3 weeks after dox treatment
• mice treated with dox at 4-6 weeks of age show PanIN, surrounded by areas of fibrosis and embedded in the acinar parenchyma after 18 weeks on dox and by 23 weeks, large areas of the pancreatic parenchyma are substituted with PanIN lesions of different grade, with frank adenocarcinoma seen in 1 of 2 mice
• mice kept on dox for 23 weeks show reversion of PanINs when dox is removed for 2 weeks
• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein, to induce acute pancreatitis, develop low- and high-grade PanIN lesions at 5 weeks after induction
• mice treated with dox 72 hours prior to induction of pancreatitis also show reversion of PanINs when dox is removed for 2 weeks
|
|
• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show impaired recovery from pancreatitis, showing acinar-ductal metaplasia with progressive accumulation of fibrotic stroma at 1 week after induction, replacement of the whole pancreatic parenchyma with ductal structures and signs of PanINs at 3 weeks after induction, and low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction compared to adult mice without dox which show completely resolved damage
• mice kept on dox for 5 weeks prior to induction of pancreatitis and then dox removal for 2 weeks show incomplete repair process resulting in a small, fibrotic pancreas with fewer acini; after 5 weeks of dox removal, no PanINs are observed however, the pancreas appears fibrotic and is small
|
|
• mice kept on dox for 5 weeks following pancreatitis induction show an increase in apoptotic cells and small pancreas size upon removal of dox
|
|
• 1 of 2 mice treated with doxycycline (dox) at 4-6 weeks of age show frank adenocarcinoma by 23 weeks on dox
• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction
|
|
• mice treated with doxycycline (dox) at 4-6 weeks of age to induce Kras2 expression begin to show low-grade pancreatic intraepithelial neoplasia (PanIN) beginning at 3 weeks after dox treatment
• mice treated with dox at 4-6 weeks of age show PanIN, surrounded by areas of fibrosis and embedded in the acinar parenchyma after 18 weeks on dox and by 23 weeks, large areas of the pancreatic parenchyma are substituted with PanIN lesions of different grade, with frank adenocarcinoma seen in 1 of 2 mice
• mice kept on dox for 23 weeks show reversion of PanINs when dox is removed for 2 weeks
• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein, to induce acute pancreatitis, develop low- and high-grade PanIN lesions at 5 weeks after induction
• mice treated with dox 72 hours prior to induction of pancreatitis also show reversion of PanINs when dox is removed for 2 weeks
|
|
• mice treated with dox at 4-6 weeks of age begin to show acinar-ductal metaplasia beginning at 3 weeks after dox treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show prolongation of the QT interval at 4 days after tamoxifen administration
• mice treated with dextromethorphan and low dose of quinidine show shortening of the prolonged QT interval
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Timothy syndrome | DOID:0060173 |
OMIM:601005 |
J:372210 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• forelimbs and hindlimbs of pups exhibit a reduction in the number of digits following doxycycline administration to dams from E4.5 to E11.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 6 of 7 mice, the tip of the mandible extends anteriorly as far as, or beyond, the tip of the maxilla
• relatively larger mandible
|
|
• in 6 of 7 mice, the tip of the mandible extends anteriorly as far as, or beyond, the tip of the maxilla
• relatively larger mandible
|
|
• in 6 of 7 mice, the tip of the mandible extends anteriorly as far as, or beyond, the tip of the maxilla
• relatively larger mandible
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Timothy syndrome | DOID:0060173 |
OMIM:601005 |
J:197612 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• during wound regeneration, RU486-treated mice exhibit YFP+ cells in the suprabasal layers but not the basal layers unlike in control mice
|
|
• in RU486-treated mice
|
|
• following treatment with RU486, plated YFP+ hair follicle stem cells do not exhibit spreading unlike YFP- cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E12 embryos
|
|
• in newborns, owing to blood pooling
|
|
• in E12 embryos
|
|
• shorter in E10 embryos
|
|
• newborn hearts have only single ventricle
|
|
• in newborns, owing to blood pooling
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only a rare number of mice survive past 5 weeks after dox treatment, with some rare survivors living at least 100 days
• more than 50% of mice show prolonged survival after dox treatment in hypoxia compared to mice in normoxia which usually die 4 weeks after treatment
|
|
• mice show increased fat body mass 2-3 weeks after dox treatment at 2-4 months of age
|
|
• dox-treated mice exhibit weight loss
• the health crisis seen 4 weeks after dox treatment is preceded by a brief period of weight loss
• however, feeding is normal
|
|
• mice show progressive decline in rotarod performance following dox-treatment
|
|
• mice show more than 50% reduction in forelimb grip strength at 25 days following termination of dox treatment
|
|
• mice show decreased rearing shortly after dox-treatment
|
|
• mice show a decline in spontaneous motor and exploratory activity level as they become moribund at around 25 days post dox-treatment
• mice show reduced total activity and reduced day and night ambulation 2-3 weeks after dox treatment
|
|
• serum succinate levels are elevated in dox-treated mice
• however, corticosteroid levels are unchanged following dox treatment
|
|
• serum glucose levels are lower at 28 days following dox treatment
|
|
• serum insulin levels are lower at 28 days following dox treatment
|
|
• serum creatine kinase is elevated in dox-treated mice, indicating muscle damage
|
|
• mice show reduced resting, active, and total energy expenditure 2-3 weeks after dox treatment
|
|
• muscle lactate levels are increased in dox-treated mice indicating muscle lactic acidosis
|
|
• mice show increased fat body mass 2-3 weeks after dox treatment at 2-4 months of age
|
|
• mice treated with doxycycline (dox) show decreases in tricarboxylic acid cycle (TCA) metabolites citrate, isocitrate, and 2-ketoglutarate in muscle
• the succinate:2-ketoglutarate ratio is increased in tissues of dox-treated mice
|
|
• muscle lactate levels are increased in dox-treated mice
• mice treated with doxycycline (dox) show decreases in tricarboxylic acid cycle (TCA) metabolites citrate, isocitrate, and 2-ketoglutarate in muscle
• however, serum lactate levels are not increased after dox treatment
|
| N |
• the few mice that live at least 100 days after dox treatment show no signs of paraganglioma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leigh disease | DOID:3652 |
OMIM:256000 |
J:284745 | |
| NOT | paraganglioma | DOID:0050773 |
OMIM:PS168000 |
J:284745 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E11.5 embryos
|
|
• in E12 embryos
|
|
• in E12.5 embryos
|
|
• diffuse vascular leakage in E11.5 embryos
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E11.5 embryos
|
|
• in E12 embryos
|
|
• in E12.5 embryos
|
|
• diffuse vascular leakage in E11.5 embryos
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E11.5 embryos
|
|
• in E12 embryos
|
|
• in E12.5 embryos
|
|
• diffuse vascular leakage in E11.5 embryos
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
• in E11.5 embryos
|
|
• starting in E9.5 embryos, worsening with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E12 embryos
|
|
• in newborns, owing to blood pooling
|
|
• in E12 embryos
|
|
• shorter in E10 embryos
|
|
• newborn hearts have only single ventricle
|
|
• in newborns, owing to blood pooling
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in E12 embryos
|
|
• in newborns, owing to blood pooling
|
|
• in E12 embryos
|
|
• shorter in E10 embryos
|
|
• newborn hearts have only single ventricle
|
|
• in newborns, owing to blood pooling
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal outflow tract septation in E9.5 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• normal outflow tract septation in E9.5 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• melanoblasts migrating along the dorsolateral pathway in hindlimb buds are not well aligned in mutants
|
|
• melanoblasts migrating along the dorsolateral pathway in hindlimb buds are not well aligned in mutants
|
|
• increase in penetrance and extent of white spotting in the posterior regions
|
|
• E10.5 mutants exhibit abnormalities of the hypoglossal nerve, with the converging roots appearing disorganized and less dense and resulting in a reduced number of elongating axons that are shorter
|
|
• E10.5 embryos exhibit the presence of fusions of dorsal root ganglia in the cervical region
|
|
• increase in penetrance and extent of white spotting in the posterior regions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• posterior pigmentation anomalies of each single mutant are accentuated in all double mutants
• lack of pigmentation in the forepaws and hindpaws
|
|
• lack of pigmentation in the distal tail
|
|
• mice exhibit hypoganglionosis
|
|
• posterior pigmentation anomalies of each single mutant are accentuated in all double mutants
• lack of pigmentation in the forepaws and hindpaws
|
|
• lack of pigmentation in the distal tail
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal steady state hematopoiesis and colony-forming capacity of hematopoietic stem and progenitor cells
|
|
• during serial transplantation
|
|
• hematopoietic stem cells exhibit enhanced expansion ex vivo and protection against loss of self-renewal capacity during serial transplantation compared with wild-type cells
• hematopoietic stem cells exhibit resistance to oxidative stress compared with wild-type cells
• however, no radioprotection is observed
|
|
• during serial transplantation
|
|
• during serial transplantation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• serotonergic innervation of the somatosensory cortex from dorsal raphe nucleus 5-HT neurons is significantly disrupted
|
|
• serotonergic innervation of the somatosensory cortex from dorsal raphe nucleus 5-HT neurons is significantly disrupted
|
|
• serotonergic innervation of the somatosensory cortex from dorsal raphe nucleus 5-HT neurons is significantly disrupted
|
|
• neither high nor low concentrations of 8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) elicit a change in baseline currents in labeled 5HT neurons
|
|
• YFP+ cells show increased spontaneous firing of action potentials
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a high number of newborns die at about P1, with very little, if any, milk in their stomach
|
|
• a subset of mutants with severe growth delay die at around P10
|
|
• newborns that die at P1 have very little, if any, milk in their stomachs
|
|
• mutants that survive past P2 exhibit severe growth delay
|
|
• 100% of mice that survive past P2 show pigmentation anomalies
|
|
• mice that survive past P2 lack pigmentation in the hindpaws
|
|
• mice that survive past P2 lack pigmentation in the distal tail
|
|
• in about 25% of surviving mice, a tiny white spot is seen on the belly
|
|
• half of newborns exhibit a kinked tail
|
|
• 100% of mice that survive past P2 show pigmentation anomalies
|
|
• mice that survive past P2 lack pigmentation in the hindpaws
|
|
• mice that survive past P2 lack pigmentation in the distal tail
|
|
• in about 25% of surviving mice, a tiny white spot is seen on the belly
|
|
• about half of mice that die at P10 exhibit hydronephrotic kidney
|
|
• mice exhibit reproduction problems
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when cre expression is suppressed by doxycycline treatment until 1 month of age the marrow cavity is decreased
|
|
• when cre expression is suppressed by doxycycline treatment until 1 month of age mice show very high bone mass 3 weeks after stopping doxycycline treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later bone mass is reduced compared to mutant mice with one wild-type Rptor allele
|
|
• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later bone marrow cavity is larger than in mutant mice with one wild-type Rptor allele but still smaller than in controls not over expressing Wnt7b
|
|
• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later osteoblast number is increased
• however, unlike in mice with one wild-type Rptor osteoblast hyperactivity is reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bones are abnormally ossified and hypervascularized compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 35% of lens in adult mice have neo-vascularization with first signs of blood vessel development visible by the first week of age
|
|
• 35% of lens in adult mice have neo-vascularization with first signs of blood vessel development visible by the first week of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tamoxifen-treated mice show increased mortality
|
|
|
• tamoxifen-treated mice develop greatly enlarged heart 16 days after induction
|
|
|
• tamoxifen-treated mice exhibit impaired cardiac fuel utilization
|
|
|
• tamoxifen-treated mice develop dilated cardiomyopathy, showing increased left ventricular interior dimension, reduced fractional shortening, and decreased relative wall thickness
|
|
|
• 16 days after induction with tamoxifen, mice exhibit contractile dysfunction analogous to end-stage dilated cardiomyopathy
|
|
|
• mitochondria exhibit increased distance between cristae in the heart 9 days after induction with tamoxifen
|
|
|
• mitochondria exhibit a round in the heart 9 days after induction with tamoxifen
|
|
|
• tamoxifen-treated hearts exhibit reduced glucose oxidation rates ex vivo
|
|
|
• reduction of enzyme activities of complexes I, II, III, and IV is isolated mitochondria of ventricles from tamoxifen-treated mice
• mitochondrial protein function is compromised in hearts of tamoxifen-treated mice, with a reduction of mitochondrial aconitase activity
• however, the number and density of mitochondria are normal in hearts
|
|
|
• mitochondrial respiration rate is lower in heart 4 days after induction with tamoxifen when cardiac dysfunction is not yet observed
|
|
|
• higher levels of oxidized proteins are seen in heart mitochondria of day 9 of induction with tamoxifen
• decrease of mitochondrial oxygen consumption rate and lower mitochondrial ATP content in hearts of tamoxifen-treated mice, suggesting a reduction in oxidative phosphorylation capacity and ATP production in mitochondria
|
|
|
• tamoxifen-treated hearts exhibit a lower oleate oxidation rate ex vivo
|
|
|
• tamoxifen-treated hearts exhibit a lower oleate oxidation rate ex vivo
|
|
|
• tamoxifen-treated hearts show decreased oxygen consumption rate
|
|
|
• tamoxifen-treated mice develop dilated cardiomyopathy, showing increased left ventricular interior dimension, reduced fractional shortening, and decreased relative wall thickness
|
|
|
• 16 days after induction with tamoxifen, mice exhibit contractile dysfunction analogous to end-stage dilated cardiomyopathy
|
|
|
• tamoxifen-treated mice develop greatly enlarged heart 16 days after induction
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:227012 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• auchene growth is terminated before formation of the single bend unlike in wild-type mice
• however, the first segment is normal
|
|
• shorter, thinner, and more numerous than in wild-type mice
|
|
• at the end of the first hair cycle, all hairs are shorter and thinner than in wild-type mice
|
|
• the first segment of zigzag hairs is variable in length from 60% to 100% of wild-type hair length
• the second segment is reduced in length 50% to 60% compared to in wild-type mice
• the first and second segments are thinner than in wild-type mice
• zigzag hairs lack the third and fourth segment unlike in wild-type mice
|
|
• duration of anagen is decreased compared to in wild-type mice
• hair follicles enter catagen prematurely compared to in wild-type mice
|
|
• catagen onset occurs at P12 and is less synchronized than in wild-type mice
|
|
• telogen begins earlier than in wild-type mice
|
|
• 40 days after depilation, only sparse hair regenerate unlike in similarly treated wild-type mice
|
|
• proliferation of matrix progenitor cells abutting the dermal papilla (MPADs) and their progeny is reduced compared to in wild-type mice
• mice fail to exhibit normal hair follicle regeneration compared with wild-type mice
|
|
• the number of apoptotic cells averaged over all follicles is increased
|
|
• the number of apoptotic cells averaged over all follicles is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tamoxifen-treated mice show an increase in the electrocardiographic rate-corrected QT interval (QTc)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in a glucose tolerance test, mice show a reduction in blood glucose excursion
• however, no difference in serum glucagon or insulin levels are seen
|
|
N |
• mice show no difference in body mass
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• administration of doxycycline in the drinking water to 4 month old mice and consequent VEGF-A164 expression in podocyte of glomerulus caused proteinuria after 7 days of treatment
|
|
• administration of doxycycline in the drinking water to 4 month old mice and consequent VEGF-A164 expression in podocyte of glomerulus caused proteinuria after 7 days of treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused death in 3 out of 8 and moribund appearance in rest of animals after 5 days of treatment
|
|
• administration of doxycycline to pregnant dam starting at day E1.5 and consequent VEGF-A164 expression in all embryonic cell caused lethality at E9.5 with no primitive red blood cells in the developing yolk sac and abnormal blood island
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused edema of the face, ears and feet after 2 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused "peliosis-like" liver characterized by an extended blood filed enlarged hepatic sinusoids and a total disruption of the normal liver architecture and blood in the intestine after 5 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused a decrease in cellularity and decreased size in thymus after 5 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused enlarged lymph nodes after 5 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused a decrease in cellularity and decreased size in thymus after 5 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused erythema of the face, ears and feet after 2 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused a decrease in cellularity and decreased size in thymus after 5 days of treatment
|
|
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in all cell caused "peliosis-like" liver characterized by an extended blood filed enlarged hepatic sinusoids and a total disruption of the normal liver architecture and blood in the intestine after 5 days of treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when treated at day 2 or 3 with pIpC, the median age of death is 16 days with distended abdomens, pale footpads, hunched posture, and ruffled fur
• untreated mice exhibit a median age of death of 95 days do to the leakiness of the cre transgene
|
|
• when treated at day 2 or 3 with pIpC, spleens are 12.8-fold larger than wild-type due to increased proliferation without decreased apoptotic rates
|
|
• when treated at day 2 or 3 with pIpC, blood smears contain an abnormal presence of immature blast cells
|
|
• when treated at day 2 or 3 with pIpC, red pulp is expanded with immature myeloid cells that are 30% to 50% positive for stem cell markers
|
|
• 2.1+/-0.5x106 per ul compared to 6.4+/-1.5x106 per ul in wild-type mice when treated at day 2 or 3 with pIpC
|
|
• 15+/-3% compared to 37+/-7% in wild-type mice when treated at day 2 or 3 with pIpC
|
|
• 515+/-223x103 per ul compared to 399+/-149x103 per ul in wild-type mice when treated at day 2 or 3 with pIpC
|
|
• 90+/-68x103 per ul compared to 3.4+/-1.5x103 per ul in wild-type mice when treated at day 2 or 3 with pIpC
|
|
• when treated at day 2 or 3 with pIpC, red pulp is expanded with immature myeloid cells that are 30% to 50% positive for stem cell markers
|
|
• when treated at day 2 or 3 with pIpC, mice develop leukemias and when transplanted into recipient mice are associated with leukemic proliferation
|
|
• when treated at day 2 or 3 with pIpC, livers are 3.3-fold larger than wild-type due to increased proliferation without decreased apoptotic rates
|
|
• when treated at day 2 or 3 with pIpC, spleens are 12.8-fold larger than wild-type due to increased proliferation without decreased apoptotic rates
|
|
• when treated at day 2 or 3 with pIpC, red pulp is expanded with immature myeloid cells that are 30% to 50% positive for stem cell markers
|
|
• 90+/-68x103 per ul compared to 3.4+/-1.5x103 per ul in wild-type mice when treated at day 2 or 3 with pIpC
|
|
• when treated at day 2 or 3 with pIpC, red pulp is expanded with immature myeloid cells that are 30% to 50% positive for stem cell markers
|
|
• when treated at day 2 or 3 with pIpC, lymphoid follicles is decreased
|
|
• when treated at day 2 or 3 with pIpC, livers are 3.3-fold larger than wild-type due to increased proliferation without decreased apoptotic rates
|
|
• when treated at day 2 or 3 with pIpC, spleens are 12.8-fold larger than wild-type due to increased proliferation without decreased apoptotic rates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma
|
|
|
• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia
|
|
|
• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma
|
|
|
• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia
|
|
|
• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma
|
|
|
• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:239660 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age
• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor
|
|
|
• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age
• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor
|
|
|
• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age
• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:239660 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• forelimbs of most (7/10) E11.5 embryos have shriveled limb buds with small patches of apical ectodermal ridge (AER) as compared to controls
|
|
• hindlimb phalanges have delays in ossification that is most obvious at tips
• hindlimb digits (E18.5) are more uniform in length as compared to controls
|
|
• all embryos exhibit a transformation of digit 1 from a shorter digit with 2 phalanges to a longer digit with 3 phalanges
|
|
• hindlimb digits (E18.5) are shorter than controls
• shortened digits are reduced proportionally
|
|
• 2 embryos (2/10) have reduced numbers of digits on both forelimbs
|
|
• 1 embryo (1/10) has polydactyly on both forelimbs
• hindlimb autopods are polydactyl (6-9 digits) with soft tissue syndactyly
|
|
• hindlimbs are polydactyl (6-9 digits) with soft tissue syndactyly
|
|
• most E11.5 embryos (7/10) lack forelimbs and have only residual cartilage attached to the scapula
|
|
• size of hindlimbs is visibly increased by E11.5
|
|
• forelimbs of most (7/10) E11.5 embryos have shriveled limb buds with small patches of apical ectodermal ridge (AER) as compared to controls
|
|
• hindlimbs have reduced levels of apoptosis in anterior AER and mesoderm beginning at E11.75
• numbers of apoptotic cells in the posterior zone are reduced in limb buds
• normal anterior necrotic zone is absent
|
|
• hindlimbs have a 20% increase in mitotic index as compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen administration at E10, hindlimb digits (1/1) are nubs (ectopic pieces of cartilage)
• following tamoxifen administration at E11.5, hindlimb digits have nubs (2/2), but nubs are smaller than nubs observed at earlier time points
• following tamoxifen administration at E10, E10.5 and E11, forelimb digits exhibit nubs
• following tamoxifen administration at E11.5, forelimbs develop normally
|
|
• following tamoxifen administration at E11, hindlimb digits exhibit distal bifurcation (1/6) or have nubs (5/6)
|
|
• following tamoxifen administration at E9.5, forelimb digits exhibit digit reduction (1/3)
|
|
• following tamoxifen administration at E10.5, hindlimb digits exhibit polydactyly (3/6), exhibit distal bifurcation (1/6) or have nubs (2/6)
|
|
• following tamoxifen administration at E9.5, some embryos have no hindlimbs (1/4)
|
|
• following tamoxifen administration at E11, hindlimb digits exhibit distal bifurcation (1/6) or have nubs (5/6)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos die between E10.5 and E14.5 with all dead by E14.5
|
|
• short and misshapen
|
|
• short and misshapen
|
|
• misshapen by E12.5
|
|
• small and misshapen by E13.5
|
|
• appears bulbous
|
|
• short and misshapen
|
|
• short and misshapen
|
|
• short and misshapen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal hair cells and neurites at P1 in the cochlea
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the absence of 4OHT, mutants develop thymic lymphoma tumors
|
|
• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in regression of autochthonous thymic lymphoma, with a reduction in tumor volume to 96% and 26% of original volume, over 3 and 10 days, respectively
• regression of tumors is due to apoptosis in thymic lymphoma
• 4OHT treatment of mutants results in massive apoptosis in thymic lymphomas but not in normal thymic tissue or other tissues
• lymphoma cells contain multi-polar spindles, indicating aberrant spindle formation, resulting in mitotic arrest and rapid cell death
|
|
• in the absence of 4OHT, mutants develop thymic lymphoma tumors
|
|
• in the absence of 4OHT, mutants develop thymic lymphoma tumors
|
|
• in the absence of 4OHT, mutants develop thymic lymphoma tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume
|
|
• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume
|
|
• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume
|
|
• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 14 weeks of tamoxifen administration, neoplastic nodules form rapidly in the liver, presumably due to increased Notch1 signaling
|
|
• after 14 weeks of tamoxifen administration, neoplastic nodules form rapidly in the liver, presumably due to increased Notch1 signaling
|
|
• after 14 weeks of tamoxifen administration, neoplastic nodules form rapidly in the liver, presumably due to increased Notch1 signaling
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thinning of neural crest-derived mesenchyme in the distal outflow tract (dOFT) of E12.5 embryos, affecting the formation of the base of the aortic valve
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• boundary of the proximal outflow tract (pOFT) and distal outflow tract (dOFT) at the outflow tract bend is distrupted, with an extension of endocardium-derived mesenchyme into the dOFT cushion in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adult injection of cre-expressing virus produces an increase in intrinsic excitability of dentate gyrus neurons compared with control mice
|
|
• mice injected with a cre-expressing virus exhibit an increase in dentate gyrus neuron AMPA/NMDA ratio compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vascular smooth muscle cell abnormalities in Gt(ROSA)26Sortm3(NOTCH3*R1031C)Sat/Gt(ROSA)26Sor+ Tg(Tagln-cre)1Her/0 and Gt(ROSA)26Sortm2(NOTCH3*C455R)Sat/Gt(ROSA)26Sor+ Notch3Gt(PST033)Byg/Notch3Gt(PST033)Byg Tg(Tagln-cre)1Her/0 mice
|
• thinning of the vascular smooth muscle layers
|
|
• osmiophilic granular deposits in mice older than 12 months of age
|
|
• vascular smooth muscle cell abnormalities with intracellular inclusions and lipid droplets that get more severe with age
• thinning of the vascular smooth muscle layers
|
|
• vascular smooth muscle cell abnormalities with intracellular inclusions and lipid droplets that get more severe with age
• thinning of the vascular smooth muscle layers
|
|
• osmiophilic granular deposits in mice older than 12 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CADASIL 1 | DOID:0111035 |
OMIM:125310 |
J:171887 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice
|
|
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice
|
|
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treatment at E9.5, but not at E10.5, results in death at birth
|
|
• when tamoxifen treated at E10.5, at P2 proliferation is similar in the anterior and central lobules, unlike in wild-type mice
|
|
• a major deletion of the midbrain is seen when tamoxifen is given at E9.5, but not when given at E10.5
|
|
• a major deletion of the medial cerebellum is seen when tamoxifen is given at E9.5 but not when given at E10.5
• when given tamoxifen at E10.5, at P14 the distinction between the vermis and the hemispheres is not apparent
|
|
• when given tamoxifen at E10.5, at E12.5 the cerebellar primordium is reduced in size
• when tamoxifen treated at E10.5, development of the vermis prepyramidal fissure is delayed and the order of fissure initiation is altered
|
|
• when given tamoxifen at E10.5, at P14 cerebellar foliation patterns are disrupted
• when given tamoxifen at E13.5 or E14.5, foliation defects in adults are less severe than when tamoxifen is given at E10.5
|
|
• when tamoxifen treated at E10.5, at E18.5 the thickness of the external granule layer was 1.5-2 times greater in the mutants than in wild types
• when tamoxifen treated at E10.5, at P2 the thickness of the external granule layer is similar in the lobules IV/V and VI unlike in wild-type mice
|
|
• when tamoxifen treated at E10.5, at P2 thickness is similar to that at E18.5 and thinner than in the controls.
|
|
• when given tamoxifen at E13.5 or E14.5, in adults the preculminate fissure is absent (between I-II and III) as lobules I-III are fused
• when given tamoxifen at E10.5, at P3 the depth of the primary fissure is increased relative to the intercrural fissure
|
|
• when given tamoxifen at E10.5, at P14 the anterior region (lobules I-V) is reduced and the central region (lobules VI-VII) is preferentially expanded
|
|
• when tamoxifen is given at E10.5, at P14, unlike in wild type, the remnants of lobules I-V extend into the hemispheres
• when tamoxifen is given at E10.5, at P14 remnants of the vermis, specific anterior and posterior regions, are maintained more laterally than in wild-type
• when given tamoxifen at E10.5, at P14 in some mutants lobule VIII is diminished more medially than lobule IX rather than the opposite as occurs in wild-type
• when tamoxifen treated at E10.5, at P2 lobules I - V are smaller and lobule VI is much larger than in wild-type
• when tamoxifen is given at E13.5 or E14.5, in adults lobule VIII is shifted posterior and fused with dorsal lobule IX
• when tamoxifen treated at E10.5, at P2 the thickness of the external granule layer is similar in the lobules IV/V and VI unlike in wild-type mice
|
|
• when given tamoxifen at E10.5, at P14 lobules VI-VII occupy a greater proportion of the vermis than in wild-type
• when given tamoxifen at E10.5, at P14 lobules VIII-IX occupy a smaller proportion of the vermis than in wild-type
• when given tamoxifen at E13.5 or E14.5, in adults lobules I-III are fused into one lobule
|
|
• when tamoxifen treated at E10.5, at P2 overall size of each region, and thus total number of cells, is greatly reduced
|
|
• when given tamoxifen, at P3 the cerebellum is smaller compared to controls
|
|
• when tamoxifen treated at E10.5, at P2 proliferation is similar in the anterior and central lobules, unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• very few crossing medial olivocochlear (MOC) terminals are observed contacting outer hair cells in adult mice
|
|
• at P8, no difference in shape or organization of outer hair cells (OHCs) is observed at the apical and basal turns relative to wild-type
• morphological defects of OHCs in adults are less severe than observed in constitutive Hoxb1-deficient (Hoxb1tm1.2Fmr) mice but statistically significant loss of OHCs and moderate OHC ciliar malformations are observed
• no abnormalities are observed in basal regions
|
|
• at 3 months, threshold is pathologically elevated compared to the normal 40dB, but not as significantly as in Hoxb1tm1.2Fmr (null) mice
• thresholds are elevated at all ages tested (from 1-12 months), increasing progressively to double the control level
|
|
• at P8, no difference in shape or organization of outer hair cells (OHCs) is observed at the apical and basal turns relative to wild-type
• morphological defects of OHCs in adults are less severe than observed in constitutive Hoxb1-deficient (Hoxb1tm1.2Fmr) mice but statistically significant loss of OHCs and moderate OHC ciliar malformations are observed
• no abnormalities are observed in basal regions
|
|
• area of the ventral nucleus of the lateral lemniscus is reduced by about 50% compared to wild-type controls at P8
|
|
• specification and innervation of olivocochlear neurons is abnormal, no crossing olivocochlear (MOC) efferent neurons cross the midline at P8
• the cholinergic population of lateral olivocochlear (LOC) neurons is absent indicating defective specification
|
|
• axon pathfinding defects are observed, with ectopic r4-derived projections crossing the midline and innervating the medial nucleus of the trapezoid body (MNTB)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• very few crossing medial olivocochlear (MOC) terminals are observed contacting outer hair cells in adult mice
|
|
• at P8, no difference in shape or organization of outer hair cells (OHCs) is observed at the apical and basal turns relative to wild-type, but in adults (3 months), OHC rows are severely disorganized with loss of some hair cells in the apical turn of the cochlea; no inner hair cells (IHCs) are lost
• OHCs in the basal turns show only slight abnormalities in ciliar organization and orientation
|
|
• at 3 months, threshold is elevated to 90 dB compared to the normal 40dB
• thresholds are elevated at all ages tested (from 1-12 months), increasing progressively to double the control level
|
|
• mice raised in acoustic isolation display ABR threshold increases compared to controls, indicating that sensitivity to environmental sounds is not a significant factor
|
|
• at P8, no difference in shape or organization of outer hair cells (OHCs) is observed at the apical and basal turns relative to wild-type, but in adults (3 months), OHC rows are severely disorganized with loss of some hair cells in the apical turn of the cochlea; no inner hair cells (IHCs) are lost
• OHCs in the basal turns show only slight abnormalities in ciliar organization and orientation
|
|
• area of the ventral nucleus of the lateral lemniscus is severely reduced by about 90% compared to wild-type controls at P8
|
|
• specification and innervation of olivocochlear neurons is abnormal, no medial olivocochlear (MOC) efferent neurons cross the midline at P8
• the cholinergic population of lateral olivocochlear (LOC) neurons is very small indicating defective specification
|
|
• axon pathfinding defects are observed, with ectopic r4-derived projections crossing the midline and innervating the medial nucleus of the trapezoid body (MNTB)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are obtained in normal Mendelian ratios
|
| N |
• mice develop without phenotypic abnormalities during embryogenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following tamoxifen administration at E9.5 - E12.5, foliation pattern is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice exhibit decreased radial length, vascular density, endothelial cell proliferative activity, sprouting activity, and pericyte coverage compared with control mice
• tamoxifen-treated mice exhibit decreased vascular density in the superficial and deep vascular plexus layers compared with control mice
• tamoxifen-treated mice exhibit disorganized, regressed, disconnected and dilated retinal vessels compared with control mice
|
|
• 4-fold increased vessel leakage following oxygen-induced retinopathy in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit decreased radial length, vascular density, endothelial cell proliferative activity, sprouting activity, and pericyte coverage compared with control mice
• tamoxifen-treated mice exhibit decreased vascular density in the superficial and deep vascular plexus layers compared with control mice
• tamoxifen-treated mice exhibit disorganized, regressed, disconnected and dilated retinal vessels compared with control mice
|
|
• following oxygen-induced retinopathy, mice exhibit increased avascular area, neovascular tuft area and reduced pericyte coverage in the superficial layer with disorganized, regressed, disconnected and dilated deep layer vessels, 4-fold increased vessel leakage and 4-fold increase in multifocal hemorrhages compared with control mice
|
|
• decrease in GFAP+ cell densities in tamoxifen-treated mice
• however, the number of Pax2+ astrocytes is normal
|
|
• following oxygen-induced retinopathy, mice exhibit increased avascular area, neovascular tuft area and reduced pericyte coverage in the superficial layer with disorganized, regressed, disconnected and dilated deep layer vessels, 4-fold increased vessel leakage and 4-fold increase in multifocal hemorrhages compared with control mice
|
|
• decrease in GFAP+ cell densities in tamoxifen-treated mice
• however, the number of Pax2+ astrocytes is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adult mice develop widespread hyperplasia throughout the colonic epithelium
|
|
• hyperplasia is typified by lengthening of the crypts in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
• hyperplasia is typified by lengthening of the crypts in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following induction of expression using an adenoviral cre, mice develop lung tumors as in Krastm4Tyj
|
|
• following induction of expression using an adenoviral cre, mice develop lung tumors as in Krastm4Tyj
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with a cre-expressing adenovirus exhibit increased tumor burden due to increased lung cancer cell proliferation compared with Krastm4Tyj heterozygotes treated with a cre-expressing adenovirus
|
|
• in mice treated with a cre-expressing adenovirus
|
|
• in mice treated with a cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the formation of the epicardium is severely compromised in E12.5 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Brains of Tsc1tm1Djk/Tsc1tm1Djk Gt(ROSA)26Sortm1Sho/Gt(ROSA)26Sor+ mice injected with an adenovirus expressing cre recombinase show ventricular region abnormalities
|
• mice injected with a high dose of adenovirus expressing cre (AAVrh8-CBA-Cre) into each cerebral lateral ventricle on the day of birth exhibit a median survival of 38 days
• mice injected with a low dose of adenovirus expressing cre (AAVrh8-CBA-Cre) into each cerebral lateral ventricle on the day of birth exhibit a median survival of 180 days
• mice injected with a high dose of a different adenovirus expressing cre (AAV1-CBA-Cre) into each cerebral lateral ventricle on the day of birth exhibit a median survival of 66.5 days
|
|
• mice injected with the AAV1-CBA-Cre adenovirus exhibit signs of distress at 1-5 months of age, including hunched back, dehydration, and weight loss
|
|
• brains exhibit a smoother surface in mice injected with the AAV1-CBA-Cre adenovirus
|
|
• severe hydrocephalus in 2 of 10 and mild hydrocephalus in 6 of 10 mice injected with AAV1-CBA-Cre
|
|
• brains appear enlarged and swollen in 30 day old mice injected with the high dose of adenovirus (AAVrh8-CBA-Cre or AAV1-CBA-Cre) expressing cre
|
|
• ventricular volume at P30 is about 4 times larger in mice injected with the AAV1-CBA-Cre adenovirus, while the brain tissue volume is about 6% larger
• 3 of 4 AAV1-CBA-Cre injected mice show nodules and thickening of the ventricular lining
|
|
• massively enlarged lateral ventricles in mice injected with AAV1-CBA-Cre, resulting from a constriction between the 3rd and lateral ventricles
|
|
• mice injected with AAV1-CBA-Cre develop hypertrophy of the subependymal layer, with expansion of the normal one cell thick layer into a convoluted layer with projections and isolated nodules
|
|
• almost 2-fold increase in neuronal diameter near the periventricular area of 30 day old mice injected with the high dose of adenovirus expressing cre (AAVrh8-CBA-Cre or AAV1-CBA-Cre)
• some phospho-S6-positive Purkinje cells in the cerebellum and neurons in the caudate are enlarged in mice injected with AAV1-CBA-Cre
|
|
• mice injected with the high dose of adenovirus expressing cre (AAVrh8-CBA-Cre or AAV1-CBA-Cre) develop a hunched back
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:221022 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission
|
|
• animals become moribund at 5 weeks of age due to high lung tumor burden
|
|
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission
|
|
• animals become moribund at 5 weeks of age due to high lung tumor burden
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated and untreated mice develop widespread pancreatic intraepithelial neoplasia (PanIN) that develops from acinar cells
• PanINs proceed to more severe stages than in Krastm4Tyj/Krastm4Tyj Tg(Ela1-cre/ESR1)1Dam mice
• acinar-ductal metaplasia precedes PanIN
|
|
• tamoxifen treated and untreated mice develop widespread pancreatic intraepithelial neoplasia (PanIN) that develops from acinar cells
• PanINs proceed to more severe stages than in Krastm4Tyj/Krastm4Tyj Tg(Ela1-cre/ESR1)1Dam mice
• acinar-ductal metaplasia precedes PanIN
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with 4-hydroxytamoxifen show disruption of multiciliogenesis in lung epithelium
• 4-hydroxytamoxifen treated mice are unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium
• however, primary cilia formation occurs
|
|
• mice treated with 4-hydroxytamoxifen show disruption of multiciliogenesis in lung epithelium
• 4-hydroxytamoxifen treated mice are unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium
• however, primary cilia formation occurs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased viability in tamoxifen-treated mouse embryonic stem cells after 96 h
• however, cells exhibit no global elongation defects or decreased elongation rates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen staring at E10.5 exhibit pancreatic intraepithelial neoplasia (PanIN) that overtakes nearly all of the organ
• mice not treated with tamoxifen develop focal PanIN that are more numerous than in Krastm4Tyj/Krastm4Tyj Tg(Ipf1-cre/Esr1)35.10Dam mice
• acinar-ductal metaplasia precedes PanIN
|
|
• mice treated with tamoxifen staring at E10.5 exhibit pancreatic intraepithelial neoplasia (PanIN) that overtakes nearly all of the organ
• mice not treated with tamoxifen develop focal PanIN that are more numerous than in Krastm4Tyj/Krastm4Tyj Tg(Ipf1-cre/Esr1)35.10Dam mice
• acinar-ductal metaplasia precedes PanIN
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brown adipose tissue shows hypertrophy, accompanied by presence of large unilocular adipocytes
|
| N |
• mice shown normal glucose metabolism, with reversal of hyperglycemia to a level that is lower than in wild-type mice and normalized response to glucose challenge
|
|
• mice develop malignant sarcomas by 3 months of age at various locations of the body, including diaphragm, limb, spine, retroperitoneum, subcutaneous regions, and in the thoracic cavity
• multiple tumors of various sizes are seen in all mice
• tumors show classical biphasic neoplasm with one component of atypical lipomatous tumors and a second component of high-grade sarcoma indicating dedifferentiated liposarcoma
• tumors show heavy infiltration of inflammatory cells which are Cd45+/Ki67-
• treatment with rosigliatazone starting from 3 weeks of age prevents liposarcoma formation at 5 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1.5- and 3.3-fold in the corpus and antrum, respectively, of tamoxifen treated mice at 8 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop acinar to ductal metaplasia
|
| N |
• mice do not develop pancreatic intraepithelial neoplasia or pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• treatment with tamoxifen at E0.5 or E12 prevents the progressive photoreceptor degeneration seen in heterozygous mice without cre expression
• treatment with tamoxifen at E0.5 also rescues the hyper-autofluorescence fundus phenotype
|
|
• following tamoxifen treatment at E12 or P1and P2, at 18 weeks of age hyper-autofluorescence spots of heterogeneous size and non-uniform distribution are seen on the fundus
• tamoxifen treatment at P1 fails to rescue the fundus hyper-autofluorescence phenotype
|
|
• tamoxifen treatment at E12 or P1 and P2 results in partial rescue of progressive arteriolar narrowing at 18 weeks of age
• tamoxifen treatment at E0.5 results in complete rescue of arteriolar narrowing at 18 weeks of age
• tamoxifen treatment at P1 fails to rescue arteriolar narrowing
|
|
• only treatment with tamoxifen at E0.5 resulted in photoreceptor numbers similar to controls after P18
• mice treated with tamoxifen at E12 or P1 have fewer photoreceptors by 18 weeks of age compared to controls
|
|
• cones show a distinct trailing edge/ring-shaped shape, reminiscent of a flame instead of the normal small, round, punctate shape at E12
|
|
• treatment with a single dose of tamoxifen at P1 fails to prevent progressive retinal photoreceptor degeneration
• treatment with 2 doses of tamoxifen at P1 and P2 partially rescues the progressive retinal photoreceptor degeneration
|
|
• only treatment with tamoxifen at E0.5 resulted in photoreceptor numbers similar to controls after P18
• mice treated with tamoxifen at E12 or P1 have fewer photoreceptors by 18 weeks of age compared to controls
|
|
• cones show a distinct trailing edge/ring-shaped shape, reminiscent of a flame instead of the normal small, round, punctate shape at E12
|
|
• treatment with a single dose of tamoxifen at P1 fails to prevent progressive retinal photoreceptor degeneration
• treatment with 2 doses of tamoxifen at P1 and P2 partially rescues the progressive retinal photoreceptor degeneration
|
|
• tamoxifen treatment at E12 or P1 and P2 results in partial rescue of progressive arteriolar narrowing at 18 weeks of age
• tamoxifen treatment at E0.5 results in complete rescue of arteriolar narrowing at 18 weeks of age
• tamoxifen treatment at P1 fails to rescue arteriolar narrowing
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinitis pigmentosa 40 | DOID:0110375 |
OMIM:613801 |
J:200898 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• GFP+ PDAC cells form tumors form more metastases than GFP- PDAC cells when transplanted into recipient mice
• the highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:245611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice
|
|
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disruption of somatic innervation during development in the absence of NMDARs at P14
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, is only 151 days compared to 485 days for controls
|
|
• mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, display a significantly shorter latency of pancreatic ductal adenocarcinoma development
• all infected mice develop invasive pancreatic ductal adenocarcinoma within 10 months
|
|
• mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, display a significantly shorter latency of pancreatic ductal adenocarcinoma development
• all infected mice develop invasive pancreatic ductal adenocarcinoma within 10 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered tamoxifen at P1 show early lethality beginning at P12
|
| N |
• mice administered tamoxifen at P1fail to show frequent cranial hemorrhage or cortical brain arteriovenous malformations (bAVMs) at P14 or P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to invasive pancreatic neoplasms
|
|
• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
|
|
• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe forelimb truncation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• display severe dorsal CNS overgrowth
|
|
• display dysmorphology of the frontonasal processes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 weeks after tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit impaired erythroid development at multiple stages
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• severe in adult mice treated with tamoxifen
|
|
• cell-autonomous impairment of hematopoietic stem cell function with activation of unfolded protein response and cell death after tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit impaired erythroid development at multiple stages
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 weeks after tamoxifen treatment
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated bone marrow cells exhibit increased ER stress and increased unfolded protein response compared with control cells
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit decreased autophagic degradation with increased reactive oxygen species, mitochondrial mass, DNA damage, and enhanced cell death in hematopoietic cells unlike wild-type mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit decreased autophagic degradation with increased reactive oxygen species, mitochondrial mass, DNA damage, and enhanced cell death in hematopoietic cells unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice survive 65 days compared with Pdk1tm1Dral Gt(ROSA)26Sortm9(cre/ESR1)Arte mice that survive 57
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Reduction in islet insulin content in Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor+ Tg(Ins2-cre)23Herr/0 mice
|
• the percentage of islet area occupied by beta cells is somewhat decreased
|
|
• alpha cells are not confined to the islet mantle
|
|
• relative increase in the number of alpha cells
|
|
• some of the beta cells are irregularly shaped
|
|
• the percentage of beta cells is decreased
|
|
• reduction in islet insulin content by 5 weeks of age but not at 5 days of age
• K(sub)ATP currents in beta cells are larger compared to control cells an inhibition of these currents by glucose is impaired
• glucose induced calcium responses of beta cells are impaired
|
|
• impairment in basal and both first and second-phase glucose induced insulin secretion
|
|
• impairment in basal and both first and second-phase glucose induced insulin secretion
|
|
• elevated glucose levels develop by P3
• overt diabetes develops by 5 weeks of age
|
|
• slightly elevated
|
|
• seen in males by 4 to 6 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| permanent neonatal diabetes mellitus | DOID:0060639 |
OMIM:606176 |
J:144715 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased in doxycycline-treated mice
|
|
• doxycycline-treated mice exhibit dramatic hyper-proliferation and crypt expansion, blocked differentiation and ectopic Paneth cell production compared with control mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased in doxycycline-treated mice
|
|
• doxycycline-treated mice exhibit dramatic hyper-proliferation and crypt expansion, blocked differentiation and ectopic Paneth cell production compared with control mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal crypt proliferation, differentiation and Paneth cell production
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased in doxycycline-treated mice
|
|
• doxycycline-treated mice exhibit dramatic hyper-proliferation and crypt expansion, blocked differentiation and ectopic Paneth cell production compared with control mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
• increased in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hematopoietic progenitors at 72 hours of tamoxifen treatment show a decrease in the number of EdU+ positive cells and an increase in the G1 population, indicating an arrest in G1
|
|
• primary hematopoietic progenitors in culture treated with tamoxifen show a decrease in cell numbers over time, however an increase in cell death is not seen, indicating a cell cycle arrest
|
|
• primary hematopoietic progenitors in culture treated with tamoxifen show a decrease in cell numbers over time, however an increase in cell death is not seen, indicating a cell cycle arrest
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary brown adipocytes from tamoxifen-treated mice show a significant reduction in norepinephrine (NE)-induced uncoupled respiration relative to control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice begin to die at approximately P14
|
|
• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium
|
|
• tamoxifen-treated mice lose weight precipitously after P10
|
|
• bone marrow LSK cells cultured in methylcellulose for 9 days show significantly impaired myeloid-erythroid colony forming capability
• flow cytometric analysis indicates stagnation of erythroid differentiation at the pro-erythroblast level
• in vivo and in vitro transplantation assays show that the intrinsic capacity of hematopoietic cells is impaired in adult mice
|
|
• tamoxifen-treated mice exhibit severely reduced bone marrow cellularity at P10
|
|
• flow cytometric profiles show a reduced population of TER119+ CD71+ erythroid progenitors in fetal livers at E14.5
|
|
• tamoxifen-treated mice exhibit a significantly decreased WBC count in peripheral blood
|
|
• tamoxifen-treated mice develop lymphocytopenia in peripheral blood
|
|
• tamoxifen-treated mice show an increase in the absolute numbers of LSK cells in the bone marrow
|
|
• tamoxifen-treated mice show a significant increase in the total number of phenotypic megakaryocyte-erythroid progenitors (MEPs) in the bone marrow
• however, total numbers of common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) are not significantly altered in the bone marrow
|
|
• tamoxifen-treated mice show infiltration of inflammatory cells into the mucosal epithelium of the jejunum
|
|
• tamoxifen-treated mice exhibit a significantly decreased WBC count in peripheral blood
|
|
• tamoxifen-treated mice develop lymphocytopenia in peripheral blood
|
|
• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium
|
|
• tamoxifen-treated mice show loss of the granular layer in the epithelium of the esophagus
|
|
• tamoxifen-treated mice exhibit degeneration of the mucosal epithelium of the jejunum and infiltration with inflammatory cells
|
|
• tamoxifen-treated mice show infiltration of inflammatory cells into the mucosal epithelium of the jejunum
|
|
• tamoxifen-treated mice exhibit epidermal atrophy in skin
|
|
• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E14.5, the number of LacZ+ neural crest cell-derived cells in the skin is lower in both the head and belly regions than that in NCC-specific heterozygous knockout littermates carrying only one Resttm1.1Yasu allele
|
|
• at E14.5, the number of LacZ+ neural crest cell-derived cells in the skin is lower in both the head and belly regions than that in NCC-specific heterozygous knockout littermates carrying only one Resttm1.1Yasu allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• amacrine cells to W3B retinal ganglion cells interconnectivity is as low as in Sdk2tm1.1(cre/ERT2)Jrs homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice show delayed thymic lymphoma-mediated death and improved overall survival with a median survival of 245 days versus 195 days in oil-treated controls; 500 days after irradiation, the lymphoma-free survival 22% versus 9.4% in oil-treated controls
• however, non-irradiated tamoxifen-treated adults show no significant differences in survival up to 700 days relative to oil-treated controls
|
|
• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice exhibit a lower % of cleaved caspase-3 positive cells in their lymphomas than oil-treated controls
• although radiation-induced T cell lymphomas are largely clonogenic, thymic lymphomas of tamoxifen-treated mice are composed mainly of CD4+ CD8+ double positive cells whereas tumors in oil-treated control mice are largely composed of CD8+ single positive cells
• radiation-induced thymic lymphomas of tamoxifen-treated mice exhibit more chromosomal inversions but fewer deletion events than control tumors
|
|
• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice show a more widespread infiltration of peripheral organs (spleen, liver, kidney, and lung) by T-lymphoma cells and a higher tumor dissemination score at the time of death relative to oil-treated controls
|
|
• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice that die within the first 195 days post-irradiation show a slight reduction in the size/weight of lymphomas relative to oil-treated controls
• however, no significant difference in primary thymus tumor weight is noted at the time of death
|
|
• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice show a significant delay in the development of radiation-induced thymic lymphomas and lymphoma-mediated death relative to oil-treated controls, likely due to slower tumor enlargement in the thymus
• however, non-irradiated tamoxifen-treated adults show no obvious growth retardation or tumor development up to 700 days relative to oil-treated controls
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice show delayed thymic lymphoma-mediated death and improved overall survival with a median survival of 245 days versus 195 days in oil-treated controls; 500 days after irradiation, the lymphoma-free survival 22% versus 9.4% in oil-treated controls
• however, non-irradiated tamoxifen-treated adults show no significant differences in survival up to 700 days relative to oil-treated controls
|
|
• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice exhibit a lower percentage of cleaved caspase-3 positive cells in their lymphomas than oil-treated controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-induced mice exhibit reduced peripheral blood red blood cell numbers
|
|
• tamoxifen-induced mice exhibit reduced hematocrit
|
|
• tamoxifen-induced mice exhibit reduced hemoglobin
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unable to recover any viable embryos after E13.5
|
|
• pancreas shows absence of glucagon+ alpha cells at E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• sequential injection of tamoxifen to pregnant females at E13.5 and E14.5 to activate cre recombinase results in a pancreatic tubular epithelium devoid of endocrine and exocrine markers, indicating impaired differentiation of progenitor cells
• however, when tamoxifen is injected into adults, mature endocrine are not perturbed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe in tamoxifen-treated mice without beta-cell apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in of all doxycycline-treated mice arising from neural crest-lineage cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice die postnatally
• however, most mice are alive at 2 months
|
|
• mice that die exhibit the same phenotype as Tfrctm3.1Nca/Tfrctm3.1Nca Tg(Vil-cre)20Syr mice
• however, mice that survive at 2 months exhibit normal architecture and proliferation of crypt intestinal epithelial cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdpk1tm1Dral homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• in doxycycline-treated mice
|
|
|
• doxycycline-treated mice exhibit microinvasive tumors in the prostate gland unlike in Pdk1tm1Dral homozygotes
|
|
|
• doxycycline-treated mice exhibit increased proliferation in the prostate gland compared to in Pdk1tm1Dral homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• female mice exhibit a tended towards increased adiposity compared with wild-type mice
|
|
• mice exhibit increased food intake compared with wild-type mice and Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
• at 16 weeks, mice are significantly heavier than Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
• preneoplastic nodules are first detected at about 160 days of age in males
• liver nodules in quadruple transgenic mice are larger and more numerous compared to triple transgenic mice that are wild-type at the Trp53 locus
|
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice a tend towards increased in body weight compared with Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)
• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture
• blood vessel density in prostate is 1.8 fold more than in control
• increased collagen deposition at the prostatic peri-glandular spaces
• presence of reactive stroma
• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells
• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
|
• increase in number CD45+ leukocytes in prostate tissue as compared to control (lacking JAG1 over expression)
• prostate tissue in 15/16 mutant mice contains large papillary structures with complex glandular architecture
• blood vessel density in prostate is 1.8 fold more than in control
• increased collagen deposition at the prostatic peri-glandular spaces
• presence of reactive stroma
• stromal cell layer is disrupted and thinner with increased vimentin staining in peri-glandular stromal cells
• prostate tissues contain more inflammatory foci as compared to controls (lacking JAG1 overexpression)
|
|
• 62.5% mutant mice (as compared to 20% in controls lacking JAG1 overexpression) have a mass of poorly differentiated adenocarcinoma extended into lumen of seminal vesicles and replacing the normal lining of epithelium
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
|
|
• mice develop high grade prostatic intraepithelial neoplasia at 32 weeks and focal adenocarcinoma by one year
• mice develop a higher grade reactive stroma with lymphocytic infiltration as compared to control (lacking JAG1 overexpression)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:238768 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• differentiation of exocrine lineages is impaired; progenitors remain trapped in an undifferentiated state
|
|
• differentiation of exocrine lineages is impaired; progenitors remain trapped in an undifferentiated state
|
|
• differentiation of endocrine lineages is impaired; progenitors remain trapped in an undifferentiated state
|
|
• at E15.5, alpha cell numbers are reduced 8-fold
|
|
• at E15.5, beta cell numbers are reduced nearly 100-fold
|
|
• pancreatic epithelium at E17.5 is translucent, cystic and comprised of highly branched, tubular epithelium with few distinct acini
• newborn pancreas exhibits convoluted epithelium in a fibroblastic stroma instead of acinar and islet tissue
• differentiation of exocrine and endocrine progenitor cells is impaired
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining
• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells
• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice
• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo
|
|
• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice
• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected
|
| N |
• tamoxifen-treated mice fed a high-fat diet (HFD) for 12 weeks show no significant differences in HFD-induced body weight gain, fat content, leanness of body mass or fasting blood glucose levels relative to control mice, with no improvement in glucose clearance and insulin sensitivity
|
|
• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice
• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected
|
|
• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining
• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells
• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice
• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo
|
|
• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells
|
|
• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining
• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells
• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice
• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• persistent adherence of the lens vesicle to the corneal ectoderm hinders the migration of neural crest cells across the stromal space between the surface ectoderm and endothelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated murine lung fibroblasts infected with HSV-1
|
|
• in tamoxifen-treated murine lung fibroblasts infected with HSV-1
|
|
• tamoxifen-treated murine lung fibroblasts infected with HSV-1 produce less IFN-beta and IL6
• HSV-1-infected, tamoxifen-treated mice exhibit increased viral titer in the spleen or brain and increased mortality compared with control mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die at 3 weeks of age of unknown causes
|
| N |
• cochlear wiring and in spiral ganglion neuron firing properties are normal
|
|
• precocious basolateral localization of pre-synaptic ribbons in the hair cells
• however, the number of ribbons is normal
|
|
• afferent synapse development is accelerated in spiral ganglion neuron compared to in control mice
|
|
• precocious basolateral localization of pre-synaptic ribbons in the hair cells
• however, the number of ribbons is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice exhibit increased radial length (1.5-fold), vascular density (1.6-fold), vessel diameter (1.9-fold), endothelial cell proliferative activity (2.0-fold) and sprouting activity (1.8-fold) compared with control mice
|
|
• 2.4-fold decreased vessel leakage following oxygen-induced retinopathy in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit increased radial length (1.5-fold), vascular density (1.6-fold), vessel diameter (1.9-fold), endothelial cell proliferative activity (2.0-fold) and sprouting activity (1.8-fold) compared with control mice
|
|
• following oxygen-induced retinopathy, mice exhibit decreased avascular area, neovascular tuft area and increased pericyte coverage in the superficial layer with more densely networked vessels in the central and middle regions of the deep layer, 2.4-fold decreased vessel leakage and 8.6-fold decrease in multifocal hemorrhages compared with control mice
|
|
• 1.3-fold increase in GFAP+ cell densities in tamoxifen-treated mice
• however, the number of Pax2+ astrocytes is normal
|
|
• following oxygen-induced retinopathy, mice exhibit decreased avascular area, neovascular tuft area and increased pericyte coverage in the superficial layer with more densely networked vessels in the central and middle regions of the deep layer, 2.4-fold decreased vessel leakage and 8.6-fold decrease in multifocal hemorrhages compared with control mice
|
|
• 1.3-fold increase in GFAP+ cell densities in tamoxifen-treated mice
• however, the number of Pax2+ astrocytes is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following tamoxifen treatment at E8.5 at E16.5 mandible size is not significantly different from controls, indicating this does not contribute to cleft palate
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage and the hyoid primordium has a gentle M shape
|
|
• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline
• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls
|
|
• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls
• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves
|
|
• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium
|
|
• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls
|
|
• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls
• however, no defects in intrinsic muscle morphology are seen
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage and the hyoid primordium has a gentle M shape
|
|
• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage
|
|
• following tamoxifen treatment at E8.5 at E11.5 the C1 motor nerve fuses directly to the CN XII nerve in 50% of embryos but never seen in controls
|
|
• following tamoxifen treatment at E8.5 at E11.5 the C1 motor nerve fuses directly to the CN XII nerve in 50% of embryos but never seen in controls
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage
|
|
• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium
|
|
• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline
• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls
|
|
• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls
• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves
|
|
• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium
|
|
• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls
|
|
• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls
• however, no defects in intrinsic muscle morphology are seen
|
|
• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen
• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage and the hyoid primordium has a gentle M shape
|
|
• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline
• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls
|
|
• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5
|
|
• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls
• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves
|
|
• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium
|
|
• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls
|
|
• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls
• however, no defects in intrinsic muscle morphology are seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment at E8.5 at E14.5, head movements are not accompanied by detectable mouth opening or tongue movement unlike in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated KIT+ bone marrow cells exhibit increased migration in a transwell assay in vitro and increased bone marrow homing in vivo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice, especially females, are born at less than Mendelian frequency
|
|
• trend towards lower body weight
|
|
• impaired balance control at 12 weeks of age
• take three times longer than controls to turn around on a thin rod suspended above the ground, and many fell off while attempting to do so
|
|
• fall off a rotating rod earlier than control mice at 12 weeks of age
|
|
• unable to hang as long from an inverted screen or a horizontal bar at 12 weeks of age
|
|
• more spontaneous activities than controls at 12 weeks of age
• stay significantly longer than controls in free-running wheels at 12 weeks of age
• run longer distance over a 23-hour period on a free-running wheel
|
|
• more hyperpolarized resting membrane potential of cerebellar Purkinje cells in acute brain slices than in controls
• restored by tolbutamide, a specific inhibitor of KATP channels
|
|
• substantially lower action potential frequency of cerebellar Purkinje cells in acute brain slices in both cell-attached and whole-cell recordings
• restored by tolbutamide
|
|
• the ATP sensitivity of the native muscle ATP-sensitive potassium (KATP) channel is reduced compared with that of control mice in patch-clamp recordings of isolated muscle fibers
|
|
• unable to lift weights as effectively or to hang as long from an inverted screen or a horizontal bar at 12 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| permanent neonatal diabetes mellitus | DOID:0060639 |
OMIM:606176 |
J:162008 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no developmental abnormalities are detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• DNA mismatch repair (measured by cre reversion and activation of the lacZ reporter) is increased about 100 fold relative to mice heterozygous form the Pms2 allele
• average numbers of gastrointestinal tract spots (stained villi) in homozygous Pms2 mutants is 3300 compared to 26 in Pms2 heterozygotes
|
|
• DNA mismatch repair (measured by cre reversion and activation of the lacZ reporter) is increased about 100 fold relative to mice heterozygous form the Pms2 allele
• average numbers of gastrointestinal tract spots (stained villi) in homozygous Pms2 mutants is 3300 compared to 26 in Pms2 heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups lose weight, become hyperglycemic, and die by postnatal day 3 (P3)
|
| N |
• endocrine differentiation is not completely abrogated, as some chromogranin A stained cells expressing EGFP are detected; some endocrine cells express PPY, with a few expressing glucagon or coexpressing PYY, but no insulin-, somatostatin-, or PP-expressing cells are observed
|
|
• in contrast to normal pancreata where Neurog3-positive cells generate individual or pairs of duct cells, most EGFP-labeled cells are duct cells with Notch activation in 2-day old mice; no cells expressing both duct and endocrine markers are detected
• total numbers of duct cells are comparable to controls, but with Notch-activation, the fraction fated to duct lineage is substantially increased relative to cells fated to endocrine lineage
|
|
• islets fail to develop
|
|
• in contrast to normal pancreata where Neurog3-positive cells generate individual or pairs of duct cells, most EGFP-labeled cells are duct cells with Notch activation in 2-day old mice; no cells expressing both duct and endocrine markers are detected
• total numbers of duct cells are comparable to controls, but with Notch-activation, the fraction fated to duct lineage is substantially increased relative to cells fated to endocrine lineage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at E15.5
|
|
• reduced subepicardium thickness is detected at E14.5
|
|
• death is associated with pericardial bleeding (suggesting cardiac failure as cause of death)
|
|
• gaps in epicardium are usually associated with cysts and epicardial blistering
|
|
• death is associated with pericardial bleeding (suggesting cardiac failure as cause of death)
|
|
• reduced subepicardium thickness is detected at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• fate mapping of Pax3 derivatives showed normal heart septation and cellular contributions to the outflow tract in newborn pups
|
| N |
• fate mapping of Pax3 derivatives showed normal patterning of enteric ganglia in the stomach and gastrointestinal tract of newborn pups
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• X-Gal staining of E9.5 embryos showed no obvious defects in neural crest contribution to the branchial arches or craniofacial mesenchyme relative to control embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at E10.5, E14.5 and E18.5, secondary heart field development is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• neural tube defects after deletion of Nap1l2 at E9
|
|
|
• neural tube defects after deletion of Nap1l2 at E9
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• neural tube defects after deletion of Nap1l2 at E9
|
|
|
• neural tube defects after deletion of Nap1l2 at E9
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals die at birth, but viable fetuses are observed at E16.5 and E18.5; no Kit protein is detected by Western blot
|
|
• at E18.5, hearts have lower total numbers of EGFP-positive cells compared to controls and no EGFP-positive cardiomyocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10 days after sparse injection with cre-expressing virus, mice exhibit decreased spine density, spine head width and spine neck length compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as early as 2 weeks, tamoxifen-treated mice exhibit progressive, heterotopic ossification (HO) in the sternum, caudal vertebrae, hip joint and hindlimb resulting in fusion between the heterotropic bone and native skeletal elements
• mature heterotropic bone contain bone marrow and resemble normal bone
• however, treatment with broad-acting BMP and activin blockers ACVR2A-Fc and ACVR2B-Fc, alone or in combination, inhibits or ameliorates HO phenotype
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| fibrodysplasia ossificans progressiva | DOID:13374 |
OMIM:135100 |
J:234069 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in lymph node, parotid salivary gland, submandibular gland, and lacrimal gland
|
|
• in lymph node, parotid salivary gland, submandibular gland, and lacrimal gland
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• abnormal lymphatic vessels fail to extend into distal mesentery unlike in wild-type mice
• between E15.5 and E16.5, lymphatic vessels are almost completely lost unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E9.5, mice exhibit fewer progenitor cells migration into the outflow tract compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Gnrh+ neurons in the medial preoptic area and posterior hypothalamus
|
|
• in the anterior olfactory nucleus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice are produced and only remnants of embryos are detected at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals die at birth, but viable fetuses are observed at E16.5 and E18.5; no Kit protein is detected by Western blot
|
|
• at E16.5, hearts have lower total numbers of EGFP-positive cells compared to controls, and no EGFP-positive cardiomyocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of cardiac neural crest cells reaching the outflow tract is moderately reduced compared to in wild-type mice
|
|
• mice exhibit abnormal patterning of cardiac neural crest cells compared to in wild-type mice
|
|
• the number of cardiac neural crest cells reaching the outflow tract is moderately reduced compared to in wild-type mice
|
|
• mice exhibit abnormal patterning of cardiac neural crest cells compared to in wild-type mice
|
|
• the number of cardiac neural crest cells reaching the outflow tract is moderately reduced compared to in wild-type mice
|
|
• mice exhibit abnormal patterning of cardiac neural crest cells compared to in wild-type mice
|
|
• mice exhibit abnormal patterning of cardiac neural crest cells compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• transgenic cre positive animals are obtained with low frequency from crosses with Gt(ROSA)26Sortm1Sor heterozygotes, suggesting that Tg(Cck-cre)CKres carriers may have reduced survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen-treatment of cultured neural stem cells
|
|
• following tamoxifen-treatment of cultured neural stem cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 9 tamoxifen-treated mice exhibit intestinal fibrosis
|
|
• in one tamoxifen-treated mouse
|
|
• sclerotic glomeruli in tamoxifen-treated mice
|
|
• enlarged glomeruli in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in some tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at P1
|
| N |
• despite loss of crypt basal columnar cells in diphtheria-treated E15 mice, intestinal epithelium homeostasis is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• proliferation of parietal epithelial cells, not podocytes, is observed; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase
|
|
• vacuolar degeneration of parietal epithelial cells is observed after LMB2 treatment
• proliferation of parietal epithelial cells, not podocytes, is also seen; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase
|
|
• vacuolar degeneration of podocytes is observed after LMB2 treatment; podocytes are identified by lacZ staining
• podocytes are lost temporally after LMB2 treatment, correlating with progression of sclerosis
|
|
• hyalinosis is seen after LMB2 treatment
|
|
• mesangiolysis is seen after LMB2 treatment
|
|
• after treatment with the immunotoxin LMB2, transgenic animal rapidly develop glomerulosclerosis
• 18%, 23%, and 60% of glomeruli show segmental or global sclerosis at 10, 14 or 21 days after treatment, respectively
|
|
• proliferation of parietal epithelial cells, not podocytes, is observed; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• differentiation of pancreatic progenitor cells to endocrine (islet) or exocrine (acinar) lineage is blocked, and cyst-like structures form with Notch1 activation at E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutant bone marrow transplanted chimeras survive to 250 days after pI-pC treatment
• decreased numbers of CD45.2+eGFP+ DP leukemic cells in the mutant bone marrow transplanted chimeras at 3 and 12 weeks
• CD45.2+eGFP+ DP leukemic cells disappear by 24 weeks
|
|
• decreased B220+ B cell numbers
|
|
• decreased B220+ B cell numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutant bone marrow transplanted chimeras survive to 26 days after pI-pC treatment
|
|
• three weeks after pI-pC injection, the bone marrow is almost exclusively composed of CD45.2+eGFP+ DP leukemic cells in the mutant bone marrow transplanted chimeras
• infiltration of the spleens by leukemic DP cells
|
|
• severe splenomegaly in mutant bone marrow transplanted chimeras
|
|
• decreased B220+ B cell numbers in mutant bone marrow transplanted chimeras
|
|
• increased WBC counts in mutant bone marrow transplanted chimeras
|
|
• severe splenomegaly in mutant bone marrow transplanted chimeras
|
|
• decreased B220+ B cell numbers in mutant bone marrow transplanted chimeras
|
|
• increased WBC counts in mutant bone marrow transplanted chimeras
|
|
• severe splenomegaly in mutant bone marrow transplanted chimeras
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen induction in 8-week old mice did not result in observable differences in pancreatic cell types compared to controls; about 90% of EGFP-labeled (or EYFP-labeled (in Tg(Neurog3-cre/ERT2)1Able/ Gt(ROSA)26Sortm1(EYFP)Cos/+ mice) cells differentiate into insulin-expressing (chromogranin A stained) cells; differentiation is not affected in adult Neurog3-positive cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with Notch activation, about 10% of islets have EGFP-positive cells not expressing chromogranin A (ie. non-endocrine cells); most of these cells are duct cells or in small intraislet ductules at ages P2 to 1 year
• no EGFP-labeled cells express amylase, indicating they are not of acinar lineage
|
|
• most islets are histologically indistinguishable from normal littermates, but some cells in the center of islets stain for hormones normally restricted to the islet periphery but not found in the core (glucagon, somatostatin, PP) whereas in normal islets, insulin staining is uniform in the core; this change in distribution is seen in most islets in 2-day old to 1yr old animals but total numbers of non-insulin expressing cells are not significantly changed
• non-insulin expressing endocrine cells in the islet cores do not coexpress insulin or MafA, suggesting they do not have properties of mature beta cells
• about 1-2% of EGFP-labeled cells are associated with large dilated cystic structures lined with cuboidal cell; large EGFP-expressing ducts are sometimes associated with islets and small intraislet ductiles within an adjacent islet
|
| N |
• mice are normoglycemic with normal glucose tolerance
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 62% of brain slice lateral hypothalamic area (LHA) Nts +ve neurons depolarize when treated with leptin while about 20% of Nts +ve neurons respond with slow hyperpolarization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit abnormal distribution of Reck+ cells compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased CD8+ effector T cells in the peripheral blood lymphocytes compared with control mice following infection with actA- L. monocytogenes-expressing ovalbumin
• decreased CD8+ memory precursors and memory T cells compared with control mice following infection with actA- L. monocytogenes-expressing ovalbumin
|
|
• following infection with actA- L. monocytogenes-expressing ovalbumin, memory CD8+ T cells exhibit impaired maturation, function and recall response compared with control mice
|
|
• decreased CD8+ effector T cells in the peripheral blood lymphocytes compared with control mice following infection with actA- L. monocytogenes-expressing ovalbumin
• decreased CD8+ memory precursors and memory T cells compared with control mice following infection with actA- L. monocytogenes-expressing ovalbumin
|
|
• following infection with actA- L. monocytogenes-expressing ovalbumin, memory CD8+ T cells exhibit impaired maturation, function and recall response compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• smaller body weight at P24
|
|
• from 2 weeks of age, mice show progressive growth retardation
|
|
• thickened bones at 4 weeks of age
• cortices of bones are composed on woven bone in 2 month old mice
|
|
• increase in thickness of calvarial bone
|
|
• marrow space is enclosed by fibrotic cells with features of early osteoblastic precursors
|
|
• trabecular bone is composed predominately of immature woven rather than lamellar bone
• trabecular bone architecture is altered in 2 month old mice
|
|
• trabecular bone volume/tissue volume is increased by more than 6-fold in 2 month old mice
|
|
• increase in trabecular number in 2 month old mice
|
|
• decrease in trabecular spaces in 2 month old mice
|
|
• increase in trabecular bone thickness in 2 month old mice
|
|
• increase in bone mass due to increased bone formation
|
|
• generalized osteosclerotic phenotype in skulls, rib cages, tail vertebrae, and limb long bones
|
|
• from 2 weeks of age, mice show a kinky tail
|
|
• increase in thickness of calvarial bone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-injected mice show partial loss of hair cells
• organ of Corti cultures from P5 mice incubated with tamoxifen and treated with the HDAC inhibitors FK228 or SAHA show prevention of the tamoxifen-dependent degeneration of inner hair cells and outer hair cells
• treatment of P7-P9 tamoxifen-injected mice with SAHA fromP7 to P15 reduces the extent of tamoxifen-dependent hair cell loss in cochleas
|
|
• in P70-P80 mice treated with tamoxifen from P40 to P47
|
|
• mice treated with tamoxifen from P40 to P47 show hearing loss one month after treatment
• mice treated with tamoxifen from P7 to P9 show hearing loss at P16
• treatment of P7-P9 tamoxifen-injected mice with SAHA from P7 to P15 reduces the tamoxifen-dependent shift in hearing threshold at low sound frequencies
|
|
• tamoxifen-injected mice show partial loss of hair cells
• organ of Corti cultures from P5 mice incubated with tamoxifen and treated with the HDAC inhibitors FK228 or SAHA show prevention of the tamoxifen-dependent degeneration of inner hair cells and outer hair cells
• treatment of P7-P9 tamoxifen-injected mice with SAHA fromP7 to P15 reduces the extent of tamoxifen-dependent hair cell loss in cochleas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit overproduction of a proximal tubule marker
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shortened outflow tracts
|
|
• cardiac outflow tracts of E11.5 embryos show no evidence of conotruncal septation
|
|
• fewer neural crest cells are seen in post-otic and circumpharyngeal streams of E10.5 embryos
|
|
• the depth of cardiac outflow tract penetration by neural crest cells is reduced and elongation of the outflow tract apparatus is truncated in E10.5 embryos, resulting in shortened outflow tracts
|
|
• fewer neural crest cells are seen in post-otic and circumpharyngeal streams of E10.5 embryos
|
|
• the depth of cardiac outflow tract penetration by neural crest cells is reduced and elongation of the outflow tract apparatus is truncated in E10.5 embryos, resulting in shortened outflow tracts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the developing head region at E9.5
|
|
• decrease in the proportion of reporter expressing cells in the cranial region at E10.5 a some embryos
|
|
• in the developing head region at E9.5
|
|
• decrease in the proportion of reporter expressing cells in the cranial region at E10.5 a some embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop solid tumors starting at 8 months of age at various locations of the body, including diaphragm, limb, spine, retroperitoneum, and subcutaneous regions
• by 13 months of age, all mice develop tumors
• tumors are identified as dedifferentiated liposarcomas
• treatment with rosigliatazone starting at 7 months of age prevents liposarcoma formation at 15 months of age
|
|
• epididymal white adipose tissue is not visible in mice older than 5 months of age
|
|
• adipose tissues of adults, but not 3 week old mice, express lower levels of mature adipocyte markers, indicating dedifferentiation of white adipocytes
• mice treated with rosiglitazone, show reactivation of mature adipocyte marker expression
|
|
• adults gradually develop lipodystrophy, resulting in an approximate 90% reduction of adipose tissue weights
• mice treated with rosiglitazone, a synthetic Ppar-gamma ligand and antidiabetic drug, show increased size and weight of adipose tissues
|
|
• adipose tissues of adults, but not 3 week old mice, express lower levels of mature adipocyte markers, indicating dedifferentiation of white adipocytes
• mice treated with rosiglitazone, show reactivation of mature adipocyte marker expression
|
|
• mice are resistant to high-fat diet-induced body weight gain
|
|
• mice are resistant to high-fat diet-induced body weight gain
|
|
• 15-fold and 40-fold increase in circulating insulin levels under fasted and re-fed conditions, respectively
• treatment with rosigliatazone rescues the diabetes
|
|
• 15-fold and 40-fold increase in circulating insulin levels under fasted and re-fed conditions, respectively, indicating severe insulin resistance
• mice fail to respond to insulin in all time points during the 2-hour insulin tolerance tests on both a chow diet and high-fat diet
|
|
• livers show very high fat content accompanied by elevated expression levels of genes involved in lipid metabolism
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normalization of obesity phenotype seen in single Lepob homozygotes
|
|
• mice exhibit very high blood glucose levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• muscleless diaphragms
• however, pleuroperitoneal fold-derived muscle connective tissue is present and mice do not develop diaphragmatic hernias
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• males display normal fertility and no defects in spermatogenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mutants have ventricular conduction system (VCS) cellular fate maps indistinguishable from Tbx5-sufficient animals indicating that defects in conditional animals do not result from loss of VCS cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• amplitude of heart contraction is significantly reduced relative to that in control hearts
• analysis of calcium cycling and heart contraction revealed impaired calcium handling
• hearts reach the maximal calcium level slightly slower than control hearts
• rate of post-contraction calcium decrease is significantly slower than that in controls hearts
• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts
|
|
• amplitude of heart contraction is significantly reduced relative to that in control hearts
• analysis of calcium cycling and heart contraction revealed impaired calcium handling
• hearts reach the maximal calcium level slightly slower than control hearts
• rate of post-contraction calcium decrease is significantly slower than that in controls hearts
• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all but one, died within 1 day of birth
• however, the early lethality seen in single Wnk1 homozygotes does not occur
|
| N |
• unlike single Wnk1 homozygotes, heart morphology is grossly normal at E15.5
|
|
• the incidence of abnormal embryos is increased compared to controls indicating only a partial rescue
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• expression of Wnk1 in the somatic embryonic cells fails to rescue the phenotypes seen in Wnk1 null embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 13 weeks of tamoxifen treatment, mice exhibit bronchial epithelial hyperplasia unlike wild-type control mice
• however, areas of hyperplasia do not progress to cancer after 18 weeks of tamoxifen treatment
|
| N |
• areas of hyperplasia do not progress to cancer after 18 weeks of tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is increased compared to mutant mice carrying Tg(MMTV-cre)1Mam
|
|
• develop a less diverse set of tumors compared to mutant mice carrying Tg(MMTV-cre)1Mam
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 69% of mice have palpable mammary tumors at the time of death
• tumors are typically either adenosquamous carcinoma or adenomyoepithioma
• isolated lung metastases are seen in rare cases
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 69% of mice have palpable mammary tumors at the time of death
• tumors are typically either adenosquamous carcinoma or adenomyoepithioma
• isolated lung metastases are seen in rare cases
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 69% of mice have palpable mammary tumors at the time of death
• tumors are typically either adenosquamous carcinoma or adenomyoepithioma
• isolated lung metastases are seen in rare cases
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:170898 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• larger than in controls
|
|
• mice treated with tamoxifen at E10.5 exhibit increased mitotic index in mesoderm-derived para-cloacal mesenchyme compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• induction of acinar to ductal metaplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop acinar to ductal metaplasia
|
| N |
• mice do not develop pancreatic intraepithelial neoplasia or pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 48 hrs of tamoxifen treatment, no tubercle formation is observed at E12.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• phenocopies metastatic pancreatic ductal adenocarcinoma that develops in mice expressing with Krastm4Tyj activated in the pancreas
|
|
• in all mice as early as 1 month with progression in amount and grade over time
|
|
• massive induction of acinar to ductal metaplasia
|
|
• in all mice as early as 1 month with progression in amount and grade over time
|
|
• pancreatic carcinoma in situ in some mice at 9 months
|
|
• phenocopies metastatic pancreatic ductal adenocarcinoma that develops in mice expressing with Krastm4Tyj activated in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tendon elements exhibit a partial ventral to dorsal conversion with ventral cartilaginous protrusions unlike in wild-type mice
|
|
• the ventral flexure at the ankle is absent
|
|
• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice
• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice
• the flexor digitorium sublimus is flattened unlike in wild-type mice
|
|
• mice exhibit loss of muscle tissue in the ventral limb unlike wild-type mice
|
|
• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice
• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice
• the flexor digitorium sublimus is flattened unlike in wild-type mice
|
|
• mice exhibit hair on the ventral skin of the paw unlike in wild-type mice
|
|
• the ventral flexure at the ankle is absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen administration leads to death of the mouse within 90 days from small intestine carcinoma
|
|
• two days after tamoxifen administration, there is a marked expansion of YFP+ cells within the crypts of the small intestine
• cultures of these cells yields four times as many, and much larger, clonogenic colonies
• ten days after tamoxifen administration, small intestine crypts are markedly disorganized with contiguous streams of YFP+ flowing out to the villi and forming a carpet of hyperplastic and grossly dysplastic cells
• sixty days after tamoxifen administration, the small intestine is twice the normal width and has a thickened, rugous appearance
• high-grade intraepithelial neoplasia and crypt adenoma formation is observed at the microscopic level sixty days after tamoxifen administration
• all mice die from the intestinal adenocarcinoma within 90 days of tamoxifen administration
|
|
• two days after tamoxifen administration, there is a marked expansion of YFP+ cells within the crypts of the small intestine
• cultures of these cells yields four times as many, and much larger, clonogenic colonies
• ten days after tamoxifen administration, small intestine crypts are markedly disorganized with contiguous streams of YFP+ flowing out to the villi and forming a carpet of hyperplastic and grossly dysplastic cells
• sixty days after tamoxifen administration, the small intestine is twice the normal width and has a thickened, rugous appearance
• high-grade intraepithelial neoplasia and crypt adenoma formation is observed at the microscopic level sixty days after tamoxifen administration
• all mice die from the intestinal adenocarcinoma within 90 days of tamoxifen administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice do not exhibit distal airspace morphological changes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• glomeruloid lesions form when tamoxifen is administered throughout pregnancy, although these lesions are less severe than in germ line null mice
|
|
• endothelial hyper-sprouting and retention of mural cell coverage on arteries and veins are detected after tamoxifen treatment
|
|
• endothelial hyper-sprouting and retention of mural cell coverage on arteries and veins are detected after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 16 mice develop abdominal tumors at 36-56 days of age
• tumors originate from the adrenals and/or the ganglion celiacum and some mice have thoracal or superior cervical ganglion tumors
• tumors consist almost entirely of small, round blue cells, similar to human neuroblastomas and express markers of neuroblastoma
• mice treated with JQ1, a compound that downregulates expression of N-myc and suppresses N-myc-driven transcription show increased cell death and reduced proliferation of tumors
|
|
• 4 of 16 mice develop abdominal tumors at 36-56 days of age
• tumors originate from the adrenals and/or the ganglion celiacum and some mice have thoracal or superior cervical ganglion tumors
• tumors consist almost entirely of small, round blue cells, similar to human neuroblastomas and express markers of neuroblastoma
• mice treated with JQ1, a compound that downregulates expression of N-myc and suppresses N-myc-driven transcription show increased cell death and reduced proliferation of tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neuroblastoma | DOID:769 | J:241988 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with tamoxifen administration to dams from E8.5 to 14.5, embryonic lungs display abnormal shape and simplified branching (reduced number of terminal buds in accessory lobe as example)
|
|
• with tamoxifen administration to dams from E8.5 to 14.5, webbed digits are observed at level of forelimbs in embryos
|
|
• with tamoxifen administration to dams from E8.5 to 14.5, cecum length is decreased in embryos relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slower growth of horizontal blood vessels in retina at age P7 after tamoxifen administration from age P1-P4
|
|
• increased blood vessel leakage in retina at age P7 after tamoxifen administration from age P1-P4
|
|
• slower growth of horizontal blood vessels in retina at age P7 after tamoxifen administration from age P1-P4
• increased blood vessel leakage at age P7 after tamoxifen administration from age P1-P4
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| exudative vitreoretinopathy | DOID:0050535 |
OMIM:PS133780 |
J:328283 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• urea cycle metabolism is rescued
|
| N |
• kidney size and morphology are rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• urea cycle metabolism is rescued
|
| N |
• kidney size and morphology are rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slower growth of horizontal blood vessels in retina at age P3 during tamoxifen administration from age P1-P4
• slower growth of horizontal blood vessels in retina at age P9 after tamoxifen administration from age P1-P4
• delayed growth of vertical blood vessels in superficial retina vascular plexus at age P9 after tamoxifen administration from age P1-P
• lack of vertical secondary and tertiary vessels in retina at age P9 after tamoxifen administration from age P1-P4
• defects of vascular growth into deeper layers of retina at age P9 after tamoxifen administration from age P1-P4
• defects in periphery of superficial retina vascular plexus at age P13 after tamoxifen administration from age P6
• fewer vessels in retina OPL and minimal vessels in retina IPL at age P13 after tamoxifen administration from age P6
|
|
• enlarged superficial vessels in retina at age P9 after tamoxifen administration from age P1-P4
• enlarged blood vessels in brain at age P9 after tamoxifen administration from age P1-P4
|
|
• in eyes after tamoxifen administration from age P1-P4
|
|
• extensive blood leakage in brain at age P9 after tamoxifen administration from age P1-P4
|
|
• slower growth of horizontal blood vessels at age P3 during tamoxifen administration from age P1-P4
• slower growth of horizontal blood vessels and enlarged superficial vessels at age P9 after tamoxifen administration from age P1-P4
• delayed growth of vertical blood vessels in superficial retina vascular plexus at age P9 after tamoxifen administration from age P1-P4
• lack of vertical secondary and tertiary vessels at age P9 after tamoxifen administration from age P1-P4
• defects of vascular growth into deeper layers at age P9 after tamoxifen administration from age P1-P4
• defects in periphery of superficial retina vascular plexus at age P13 after tamoxifen administration from age P6
• fewer vessels in OPL and minimal vessels in IPL at age P13 after tamoxifen administration from age P6
• increased blood vessel leakage at age P9 after tamoxifen administration from age P1-P4
|
|
• slower regression after tamoxifen administration from age P1-P4
|
|
• after tamoxifen administration from age P1-P4
|
|
• most mice die by age P9 after tamoxifen administration from age P1-P4
• mice die by age P13-P14 after tamoxifen administration from age P6
|
|
• extensive blood leakage in brain at age P9 after tamoxifen administration from age P1-P4
|
|
• after tamoxifen administration from age P1-P4
|
|
• after tamoxifen administration from age P1-P4
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| exudative vitreoretinopathy | DOID:0050535 |
OMIM:PS133780 |
J:328283 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ability of the serotonin receptor 2C agonist mCPP to depolarized Pomc-expressing neurons is abolished in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 20 days after tamoxifen treatment, mice exhibit a transient increase in hippocampal neurogenesis compared with control mice
• tamoxifen-treatment increased hippocampal neurogenesis in vitro and in vivo compared with controls
• tamoxifen-treated mice exhibit premature exit of quiescence compared with control mice
• tamoxifen-treated mice exhibit loss of neurogenic capacity of adult neurospheres and decreased neurogenesis over time compared with control mice
• neurospheres treated from tamoxifen-treated mice exhibit reduced self-renewal capacity compared with wild-type cells
• however, hippocampal neurogenesis is normal 10 and 30 days after tamoxifen treatment
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit decreased adult-generated immature and mature granule neurons compared with control mice
|
|
• 20 days after tamoxifen treatment, mice exhibit a transient increase in hippocampal neurogenesis compared with control mice
• tamoxifen-treatment increased hippocampal neurogenesis in vitro and in vivo compared with controls
• tamoxifen-treated mice exhibit premature exit of quiescence compared with control mice
• tamoxifen-treated mice exhibit loss of neurogenic capacity of adult neurospheres and decreased neurogenesis over time compared with control mice
• neurospheres treated from tamoxifen-treated mice exhibit reduced self-renewal capacity compared with wild-type cells
• however, hippocampal neurogenesis is normal 10 and 30 days after tamoxifen treatment
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 20-fold 7 days after tamoxifen-treatment
|
|
• in tamoxifen-treated mice
• however, LPS-induced proliferation is normal and treatment with Syk-specific inhibitor R406 abolishes proliferation
|
|
• 3 and 7 days after tamoxifen treatment
• however, spleen size is restored by 14 days post-induction
|
|
• B cells from tamoxifen-treated mice undergo terminal differentiation into short-lived B cells
|
|
• CD19+ B cells in tamoxifen-treated mice
• however, the increased numbers is followed by a decrease
|
|
• 20-fold 7 days after tamoxifen-treatment
|
|
• increased serum levels of monocyte chemoattractant protein-1, peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• 3 and 7 days after tamoxifen treatment
|
|
• in follicular B cells after tamoxifen-treatment
|
|
• in follicular B cells after tamoxifen-treatment
|
|
• in follicular B cells after tamoxifen-treatment
|
|
• increased serum levels of monocyte chemoattractant protein-1, peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• peaking at days 3 to 5 after tamoxifen-treatment
|
|
• 20-fold 7 days after tamoxifen-treatment
|
|
• in tamoxifen-treated mice
• however, LPS-induced proliferation is normal and treatment with Syk-specific inhibitor R406 abolishes proliferation
|
|
• 20-fold 7 days after tamoxifen-treatment
|
|
• in tamoxifen-treated mice
• however, LPS-induced proliferation is normal and treatment with Syk-specific inhibitor R406 abolishes proliferation
|
|
• 3 and 7 days after tamoxifen treatment
• however, spleen size is restored by 14 days post-induction
|
|
• B cells from tamoxifen-treated mice undergo terminal differentiation into short-lived B cells
|
|
• CD19+ B cells in tamoxifen-treated mice
• however, the increased numbers is followed by a decrease
|
|
• 20-fold 7 days after tamoxifen-treatment
|
|
• 3 and 7 days after tamoxifen treatment
• however, spleen size is restored by 14 days post-induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit a normal life span
|
|
• hepatocytes exhibit fine vacuolization unlike in wild-type mice but are otherwise normal
|
|
• moderate and in a microvesicular pattern
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at 6 to 8 weeks of age
|
|
• at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice
• livers exhibit vascular lesions observed in Vhltm1Jae/Vhltm1Jae Tg(Alb-cre)21Mgn mice with minimal evidence of vacuolization
• hepatic vascularity is increased compared to in wild-type mice
|
|
• at 6 weeks of age
|
|
• minimal
|
|
• hepatic vascularity is increased compared to in wild-type mice
|
| N |
• unlike in Vhltm1Jae/Vhltm1Jae Tg(Alb-cre)21Mgn mice, body weight is normal
|
|
• at 6 weeks of age
|
|
• of paws and unfurred skin by 4 to 6 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cell development is blocked at pro-B cell stage
|
|
• in the spleen, inguinal lymph nodes, and peritoneal cavity
|
|
• B cell development is blocked at pro-B cell stage
|
|
• slightly
|
|
• in the spleen, inguinal lymph nodes, and peritoneal cavity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe after tamoxifen treatment
|
|
• B cells from tamoxifen-treated mice undergo terminal differentiation into short-lived B cells
|
|
• prolonged survival and reduced apoptosis of plasma cells after tamoxifen treatment
|
|
• severe after tamoxifen treatment
|
|
• severe after tamoxifen treatment
|
|
• B cells from tamoxifen-treated mice undergo terminal differentiation into short-lived B cells
|
|
• prolonged survival and reduced apoptosis of plasma cells after tamoxifen treatment
|
|
• severe after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of dilated dermal blood vessels is increased compared to in wild-type mice
|
|
• following application of an inflammatory stimuli
|
|
• at weaning mice are runted
|
|
• keratinocyte proliferation is increased
|
|
• at P5
|
|
• keratinocyte proliferation is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• beta cells are reprogrammed to alpha cells
|
|
• beta cells are reprogrammed to alpha cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen at 3 weeks of age exhibit beta cells to alpha cells reprogramming
|
|
• mice treated with tamoxifen at 3 weeks of age exhibit beta cells to alpha cells reprogramming
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in smaller fiber diameters
|
|
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in diaphragms from 6 out of 18 mice that exhibit myofibers with greater than 10% central nuclei
|
|
• high dose (150 mg/kg) administration of tamoxifen by oral gavage results in severe muscle degeneration in skeletal muscle within 7-9 days
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in damage to tibialis anterior, gastrocnemius, quadriceps and triceps within 4 weeks
• at 0.5mg/kg tamoxifen administration results in a decrease in mild sporadic lesions beginning at 1 month, with a dramatic increase in severity by 3 and 4 months
|
|
• TA muscles in uninduced 1.5 year old mice are 33% smaller than controls with reduced absolute force output
|
|
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in muscle weakness
• TA muscles in uninduced 1.5 year old mice develop reduced absolute force output
|
|
• high dose (150 mg/kg) administration of tamoxifen by oral gavage results in immune cell infiltrates in skeletal muscle within 7-9 days
|
|
• administration of tamoxifen (high dose - 150 mg/kg) by oral gavage results in a slow, unsteady gait, by 10 days mice are non-ambulatory
• administration of tamoxifen (medium dose - 5 mg/kg) by oral gavage results in gait changes within 3 weeks
|
|
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in a reduction in rearing frequency
|
|
• high dose (150 mg/kg) administration of tamoxifen by oral gavage results in a reduction in overall activity, by 10 days mice are non-ambulatory
• medium dose (5 mg/kg x 3 days/week) administration of tamoxifen by oral gavage results in a reduction in total activity
• at 0.5mg/kg tamoxifen administration results in a decrease in activity beginning at 1 month, with significant reduction by 2 months, however mice recover to wild-type levels by 3-4 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| facioscapulohumeral muscular dystrophy | DOID:11727 | J:268959 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• less than 3% of the expected 25% of mutant pups are born and those pups then die immediately
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts
|
|
• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls
• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias
|
|
• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)
• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts
|
|
• TAM-treated mice show a progressive loss of OLFM4+ intestinal stem cells (ISCs) and early progenitors (seen both at 10-12 days and at 17+ days but not at 5-7 days after a single TAM injection), along with an increase in the numbers of Paneth cells and goblet cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a modest increase in the fraction stem cells (35.34% vs 22.96% in controls), fewer transit-amplifying progenitors (18.40% vs 25.73% in controls) and a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls), along with a weakened Lgr5+ stemness signature in ISCs but only minor effects on proliferation and apoptosis
• 12 days after a single TAM injection, crypt cells show induction of Atoh1 mRNA transcripts and reduction of Hes1 mRNA transcripts by ISH
• 17 days after a single TAM injection, no change in the proliferation or apoptosis of ISCs and progenitors is observed, and small intestine length, crypt depth, and numbers of chromogranin A+ enteroendocrine cells in jejunal crypts are normal
• TAM-treated mice show reduced numbers of H3K27ac-positive and Notch intracellular domain (NICD)-positive crypt cell nuclei, indicating increased class I histone deacetylase (HDAC) activity and less Notch signaling
• TAM treatment followed by administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of H3K27ac-positive and NICD-positive crypt cell nuclei to wild-type numbers
|
|
• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed control mice, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury
|
|
• when mice are treated with TAM 1 day prior to radiation-induced intestinal epithelial injury, ISCs generate 5-fold less labeled tdTomato+ crypts with fewer Lgr5+ ISC-derived labeled progeny extending up crypt-villous units at 5 days post-radiation, and the overall number of surviving intact jejunal crypts is reduced by 2-fold
• oral administration of poly(lactic-co-glycolic acid) (PLGA) encapsulated beta-hydroxybutyrate (beta-OHB) nanoparticles or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury
|
|
• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)
• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts
|
|
• TAM-treated mice show a progressive loss of OLFM4+ intestinal stem cells (ISCs) and early progenitors (seen both at 10-12 days and at 17+ days but not at 5-7 days after a single TAM injection), along with an increase in the numbers of Paneth cells and goblet cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a modest increase in the fraction stem cells (35.34% vs 22.96% in controls), fewer transit-amplifying progenitors (18.40% vs 25.73% in controls) and a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls), along with a weakened Lgr5+ stemness signature in ISCs but only minor effects on proliferation and apoptosis
• 12 days after a single TAM injection, crypt cells show induction of Atoh1 mRNA transcripts and reduction of Hes1 mRNA transcripts by ISH
• 17 days after a single TAM injection, no change in the proliferation or apoptosis of ISCs and progenitors is observed, and small intestine length, crypt depth, and numbers of chromogranin A+ enteroendocrine cells in jejunal crypts are normal
• TAM-treated mice show reduced numbers of H3K27ac-positive and Notch intracellular domain (NICD)-positive crypt cell nuclei, indicating increased class I histone deacetylase (HDAC) activity and less Notch signaling
• TAM treatment followed by administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of H3K27ac-positive and NICD-positive crypt cell nuclei to wild-type numbers
|
|
• mice treated with TAM 1 day prior to radiation-induced intestinal epithelial injury show impaired Lgr5+ ISC-mediated repair in jejunal crypts relative to controls
• oral administration of nanoparticle PLGA-encapsulated beta-OHB or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage
• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed controls, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury
|
|
• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts
|
|
• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls
• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in some dTomato-positive tail melanoblasts at P0
|
|
• in some dTomato-positive tail melanoblasts at P0
|
|
• some dTomato-positive melanoblasts exhibit fragmentating indicating cell death unlike in control mice
|
|
• some dTomato-positive melanoblasts exhibit fragmentating indicating cell death unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop abdominal tumors with an incidence of 76%
• tumor onset occurs between 26-337 days of age, with a mean age of 79.6 days
• tumors arise from the superior cervical ganglion, the adrenals, or the celiac ganglion
• histology indicates small round cell tumor with cells harboring neurosecretory vesicles and express markers indicative of neuroblastoma
• neuroblastomas are characterized by genomic aberrations syntenic to human neuroblastomas
|
|
• hyperplastic cells are present in the adrenal medulla of some adrenal glands in 0-day old pups and most 14 and 28 day old mice
• at 28 days of age, the adrenal medulla has an atypical, nodal tissue architecture
|
|
• mice develop abdominal tumors with an incidence of 76%
• tumor onset occurs between 26-337 days of age, with a mean age of 79.6 days
• tumors arise from the superior cervical ganglion, the adrenals, or the celiac ganglion
• histology indicates small round cell tumor with cells harboring neurosecretory vesicles and express markers indicative of neuroblastoma
• neuroblastomas are characterized by genomic aberrations syntenic to human neuroblastomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neuroblastoma | DOID:769 | J:222527 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reach 90% lethality by about 90 days after tamoxifen treatment
|
|
• mice begin to die 40 days after tamoxifen treatment with 90% lethality by about 90 days after treatment
|
|
• about 6 weeks after tamoxifen treatment major vascular branches of the ear are dilated and reddened and medium-sized blood vessels are scattered in the subendocardial layer
• after tamoxifen treatment, liver sections show an increase in large vessels
|
|
• after tamoxifen treatment the trachea contains more capillaries which are more branched and enlarged
• after tamoxifen treatment capillaries amid cardiac fibers are enlarged as are capillaries in the renal glomeruli
|
|
• dilated vessels and enlarged glomerular capillaries after tamoxifen treatment
|
|
• sinusoids are dilated after tamoxifen treatment
|
|
• after tamoxifen treatment the size and number of blood vessels in the lung is increased
|
|
• after tamoxifen treatment increased numbers of blood vessels are seen in the dermal and subcutaneous layers of the ear, the trachea contains more capillaries which are more branched and enlarged, more medium sized vessels are present in the subendocardial layer of the heart, and more vessels are seen in the liver and brain
|
|
• about 6 weeks after tamoxifen treatment vessels in the ear, trachea, heart, lung, kidney cortex and glomeruli, liver
• in the lung vessel dilation is accompanied by packed erythrocytes
• in the liver central veins are about 4-times larger than in controls
|
|
• significant increase in hematopoietic stem cells in the liver and spleen after tamoxifen treatment
• increase in the number of colonies formed by spleen and liver cells in a methylcellulose colony forming assay after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• dramatic increase after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• increase in the number of erythroid progenitor and myeloid cells after tamoxifen treatment
|
|
• more strongly colored than controls after tamoxifen treatment
|
|
• sinusoids are dilated after tamoxifen treatment
|
|
• dilated vessels and enlarged glomerular capillaries after tamoxifen treatment
|
|
• glomeruli are enlarged and their capillaries are dilated
|
|
• 230-fold increase in serum erythropoietin levels within 2 weeks of tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• increase in the number of erythroid progenitor and myeloid cells after tamoxifen treatment
|
|
• after tamoxifen treatment the size and number of blood vessels in the lung is increased
|
|
• erythemia is more apparent than in Egln2tm1Fong Egln3tm1Fong double homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• skeletal muscle exhibits pinch injury-induced heterotopic ossification
|
|
• spontaneous heterotopic ossification is seen infrequently in some 2-week-old mice and is present in all 4-week-old mice and extensive in all surviving mice by 6 weeks of age
• heterotopic ossification is seen in the musculature, tendons, and ligaments at diverse locations
• skeletal elements resulting from spontaneous heterotopic ossification are derived almost exclusively from recombined cells
• all mice treated with an anti-activin A mAb prior to onset of heterotopic ossification for 4 weeks survive to 6 weeks of age and 8 of 9 mice show no evidence of heterotopic ossification and no spontaneous heterotopic ossification is not seen in treated 16-week-old mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| fibrodysplasia ossificans progressiva | DOID:13374 |
OMIM:135100 |
J:257905 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• in diphtheria-treated mice
|
|
|
• in diphtheria-treated mice
|
|
|
• in diphtheria-treated mice
|
|
|
• in diphtheria-treated mice
|
|
• diphtheria-treated mice exhibit ablation of Kiss1+ neurons
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• diphtheria-treated mice exhibit normal ovalutory cyclicity and fertility
|
|
• diphtheria-treated mice exhibit ablation of Kiss1r+ and gonadotrophin-releasing hormone neurons
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit loss of muscle tissue in the ventral limb unlike wild-type mice
|
|
• the ventral flexure at the ankle is absent
|
|
• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice
• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice
• the flexor digitorium sublimus is flattened unlike in wild-type mice
|
|
• mice exhibit loss of muscle tissue in the ventral limb unlike wild-type mice
|
|
• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice
• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice
• the flexor digitorium sublimus is flattened unlike in wild-type mice
|
|
• mice exhibit hair on the ventral skin of the paw unlike in wild-type mice
|
|
• the ventral flexure at the ankle is absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• around E10.5
|
|
• severe developmental defects at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mouse embryonic fibroblasts or adult tail tip fibroblasts perform normally in embryoid body differentiation assays in terms of the formation of embryoid bodies, beating cardiomyocyes, sprouting vascular endothelial channels, or their hematopoietic differentiation potential
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer IL9+ cells in IFN-alpha-treated mice following differentiation towards Th9 lineage
|
|
• fewer IL9+ cells in IFN-alpha-treated mice following differentiation towards Th9 lineage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• variable
|
|
• cephalic hemorrhage at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are born in Mendelian ratios and show no overt phenotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when the cre transgene is inherited maternally, embryos survive to birth, regardless of the presence of the Cre transgene
|
|
• when the cre transgene is inherited paternally, embryos do not survive past E13.5
|
| N |
• when the cre transgene is inherited maternally, no PNS-related phenotypes are observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos die predominantly at E13.5, similar to embryos homozygous for the Adgrg6em2Jlp allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos are viable and show normal heart development at E10.5, E13.5 and E16.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells exhibit altered chromosome architecture genome wide in tamoxifen-treated mice
|
|
• B cells in vitro stimulated with tamoxifen exhibit a defect in class-switch recombination
• tamoxifen-treated B cells show a reduction to class-switch recombination to IgG1
• tamoxifen-treated mice show an increase in microhomology-mediated DNA junctions in B cells
|
|
• B cells exhibit altered chromosome architecture genome wide in tamoxifen-treated mice
|
|
• B cells in vitro stimulated with tamoxifen exhibit a defect in class-switch recombination
• tamoxifen-treated B cells show a reduction to class-switch recombination to IgG1
• tamoxifen-treated mice show an increase in microhomology-mediated DNA junctions in B cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Gt(ROSA)26Sortm1Lma/Gt(ROSA)26Sor+ Shhtm2(cre/ERT2)Cjt/Shhtm2(cre/ERT2)Cjt mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are born in Mendelian ratios but do not survive beyond 8 to 10 weeks
|
|
• abnormal alimentary canal, ranging from severely swollen stomachs to blackened hindguts
|
|
• blackened hindguts in some mice
|
|
• severely swollen in some mice
|
|
• mice become malnourished
|
| N |
• cell proliferation and survival are normal in the cerebellum
|
|
• GFAP+ and S100B+ without a change in proliferation or apoptosis rates
|
|
• GFAP+ and S100B+ without a change in proliferation or apoptosis rates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal GFAP+ and S100B+ astrocytes cell numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• aberrant foot print angles, irregular and reduced stride lengths
|
|
• parallel fibers accumulate unreleased synaptic vesicles unlike in wild-type cells
|
|
• stimulation of parallel fibers fails to stimulate an excitatory postsynaptic current (EPSC) unlike in similarly treated wild-type mice
• however, extremely high stimulus intensities evoke an EPSC and stimulated parallel fibers propagate action potentials normally
|
|
• mice exhibit auditory defects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit no gross functional defects in mature T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• intestinal tumors are increased in number compared to in ApcMin/Apc+ Tg(Vil-cre)20Syr
|
|
• intestinal tumors exhibit increased cell proliferation compared to in ApcMin/Apc+ Tg(Vil-cre)20Syr
|
|
• intestinal tumors exhibit increased size compared to in ApcMin/Apc+ Tg(Vil-cre)20Syr
|
|
• intestinal tumors are increased in number compared to in ApcMin/Apc+ Tg(Vil-cre)20Syr
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal percentages and total cell numbers of double positive or single positive thymocytes and CD4+ or CD8+ peripheral T cells in the spleen
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated and stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• systemic inflammation
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• no spermatozoa in epididymides
|
|
|
• impaired acrosome development and failure to produce elongated spermatids
|
|
|
• with increased mitochondria content
|
|
|
• 4-fold increase in tubules
|
|
|
|
|
|
• no spermatozoa in epididymides
|
|
|
• impaired acrosome development and failure to produce elongated spermatids
|
|
|
• with increased mitochondria content
|
|
|
• in round spermatids and giant cells
|
|
|
• in round spermatids and giant cells with aberrant accumulation of autophagic structures
|
|
|
• 4-fold increase in tubules
|
|
|
• in round spermatids and giant cells with aberrant accumulation of autophagic structures
|
|
|
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disruption of somatic innervation during development in the absence of NMDARs at P14
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal GFAP+ and S100B+ astrocytes cell numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 19 months after infection with RCASBP(A)-KrasG12D retrovirus 3 of 5 mice developed invasive and metastatic pancreatic ductal adenocarcinomas with 2 of the 5 developing liver and lymph node metastases
• all pancreatic ductal adenocarcinomas display a ductal phenotype, an intense desmoplastic stroma and local infiltration
|
|
• 9 months after infection with RCASBP(A)-KrasG12D retrovirus 4 of 5 mice developed focal ductal pancreatic lesions that closely resembled human pancreatic intraepithelial neoplasias
|
|
• 9 months after infection with RCASBP(A)-KrasG12D retrovirus 4 of 5 mice developed focal ductal pancreatic lesions that closely resembled human pancreatic intraepithelial neoplasias
• 19 months after infection with RCASBP(A)-KrasG12D retrovirus 3 of 5 mice developed invasive and metastatic pancreatic ductal adenocarcinomas with 2 of the 5 developing liver and lymph node metastases
• all pancreatic ductal adenocarcinomas display a ductal phenotype, an intense desmoplastic stroma and local infiltration
|
|
• 19 months after infection with RCASBP(A)-KrasG12D retrovirus 3 of 5 mice developed invasive and metastatic pancreatic ductal adenocarcinomas with 2 of the 5 developing liver and lymph node metastases
• all pancreatic ductal adenocarcinomas display a ductal phenotype, an intense desmoplastic stroma and local infiltration
|
|
• 9 months after infection with RCASBP(A)-KrasG12D retrovirus 4 of 5 mice developed focal ductal pancreatic lesions that closely resembled human pancreatic intraepithelial neoplasias
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when tamoxifen is administered at E12.5, mutant kidneys have about half the number of glomeruli (48%) at E19.5
• glomerulus number does not recover as well as kidney size with numbers only 57.6% of normal at P50
|
|
• when tamoxifen is administered at E12.5, fetuses develop severe renal hypoplasia by E14.5, with kidney growth rate reduced relative to wild-type
• nephrogenic zone appears normal at E19.5
|
|
• when tamoxifen is administered at E12.5, at E19.5 kidneys are 55.7% of normal size (based on maximal cross-sectional area); normal gross organization into cortex, medulla and papilla remains
• recovery from tamoxifen treatment at E12.5 is observed postnatally with kidney size reaching 70.4% of control size at P14 and 89.3% at P50
• with tamoxifen treatment at E14.5, resulting kidney morphology is similar at birth with reduced hypoplasia; kidneys are 89% of control size
• when tamoxifen is administered at E9.5, about half the fetuses have severe renal hypoplasia with kidneys about 46.6% of the size of controls
|
|
• when tamoxifen is administered at E9.5, about half the fetuses display renal agenesis at E18.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when mice are fed with a glucose-supplemented chow diet for 2 weeks and treated with TAM prior to radiation-induced intestinal injury, the ability of ISCs to generate tdTomato+ labeled progeny is reduced by 2-fold while the overall number of surviving intact jejunal crypts is significantly decreased at 3 days post-radiation
• a single oral bolus of beta-hydroxybutyrate (beta-OHB) 16 h prior to irradiation rescues these functional deficits
|
|
• when mice are fed with a glucose-supplemented chow diet for 2 weeks and treated with TAM prior to radiation-induced intestinal injury, the ability of intestinal stem cells (ISCs) to generate tdTomato+ labeled progeny is reduced by 2-fold while the overall number of surviving intact jejunal crypts is significantly decreased at 3 days post-radiation
• a single oral bolus of beta-hydroxybutyrate (beta-OHB) 16 h prior to irradiation rescues these functional deficits
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice delivered by Caesarian section do not survive beyond 24 hours after birth
|
| N |
• mice exhibit normal epidermal skin barrier function
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• complete absence of palatal bones in all mice
|
|
• complete cleft is seen in 9 of 14
|
|
• in 5 of 14
• manifests as fused anterior palate and cleft soft palate
|
|
• complete absence of palatal bones in all mice
|
|
• complete absence of palatal bones in all mice
|
|
• complete cleft is seen in 9 of 14
|
|
• in 5 of 14
• manifests as fused anterior palate and cleft soft palate
|
|
• complete absence of palatal bones in all mice
|
|
• complete cleft is seen in 9 of 14
|
|
• in 5 of 14
• manifests as fused anterior palate and cleft soft palate
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pinch injury of adult hindlimb skeletal muscle results in heterotopic ossification in 100% of mice; heterotopic skeletal lesions show that lesional tissue is typically embedded in muscle and associated soft tissues, although close apposition or fusion with limb skeletal elements is sometimes seen
• cardiotoxin-mediated injury of skeletal muscle also results in heterotopic ossification, except that this less localized injury stimulus sometimes results in tendon/ligament heterotopic ossification
• unlike in controls, regenerated muscle fibers are rarely seen in areas of lesion formation at 6 days post-injury, and instead injured muscle contains large numbers of chondrocytes and accumulations of fibroblastic cells
• by 14 days post-injury, most cartilage is replaced by bone instead of regenerated muscle fibers as in controls
• activin A injection lowers the threshold for injury-induced heterotopic ossification
• treatment with anti-activin A mAb effectively blocks injury-induced heterotopic ossification
|
|
• spontaneous heterotopic ossification is seen as early as 5.5 months of age, and by 1 year of age, 12 of 15 mice develop spontaneous heterotopic ossification
• fibro/adipogenic progenitors represent the predominant cell-of-origin for both heterotopic cartilage and bone
• pinch injury or cardiotoxin-mediated injury of adult hindlimb skeletal muscle results in heterotopic ossification in 100% of mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| fibrodysplasia ossificans progressiva | DOID:13374 |
OMIM:135100 |
J:257905 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant increase of the number of differentiated MbDA neurons at E11.5
• significant increase in the number of Ki67+ progenitors in the differentiating zone in medial planes
|
|
• depletion of medial MbDA neurons and expansion of more laterally positioned MbDA neurons at E12.5
|
|
• depletion of medial MbDA neurons
|
|
• significant increase of the number of differentiated MbDA neurons at E11.5
• significant increase in the number of Ki67+ progenitors in the differentiating zone in medial planes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos do not survive beyond around E11.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased actin aggregation in the adherens-junction region and expansion of the apical surface
|
|
• no distinguishable stereocilia
|
|
• reduction in stereocilia diameter and length eventually followed by disappearance
|
|
• ruptures
|
|
• disrupted hair cell in some bundles
|
|
• with decreased width
|
|
• no distinguishable stereocilia
|
|
• reduction in stereocilia diameter and length eventually followed by disappearance
|
|
• disrupted hair cell in some bundles
|
|
• with decreased width
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• biophysical properties of cholinergic neurons are normal
|
|
• melanotan II fails to hyperpolarize membrane potentials of all dorsal motor nucleus vagal cholinergic neurons
• similar results with Mc4r agonist THIQ
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with increased surface area and branching points in the retinal inner plexiform layer of mice treated with tamoxifen from P1 to P4
• in the retinal tissue between the inner plexiform layer and ganglion cell layer of mice treated with tamoxifen from P1 to P4
• in the retinal inner and outer plexiform layer, lung, heart, brain, kidney, liver and cornea of mice treated with tamoxifen as adults
• after left anterior descending coronary artery ligation in tamoxifen-treated mice
• the retina of neonates treated with tamoxifen exhibit increased tip cells by P5 compared with control mice
• however, tamoxifen-treated mice exhibit normal vascular maturation and perfusion
|
|
• 8 weeks after left anterior descending coronary artery ligation, tamoxifen-treated mice exhibit decreased infarct area and increase in PECAM-1 positive vessels in infarcted and non-infarcted areas compared with control mice
|
|
• in tamoxifen treated mice exposed to high concentration of VEGF-A
• however, permeability is normal without VEGF-A treatment or with the addition of SU1498 (anti-VEGF-A inhibitor)
|
|
• in the retina (ganglion cell layer and inner and outer plexiform layer) of tamoxifen-treated mice at P21
|
|
• at P21 in mice treated with tamoxifen as neonates
• however, mice treated with tamoxifen as adults are not visibly different from wild-type mice
|
|
• at P21 in the liver of tamoxifen-treated mice
• however, tamoxifen-treated mice subjected to left anterior descending coronary artery ligation exhibit normal macrophage numbers in the infarcted myocardium
|
|
• 8 weeks after left anterior descending coronary artery ligation, tamoxifen-treated mice exhibit decreased infarct area and increase in PECAM-1 positive vessels in infarcted and non-infarcted areas compared with control mice
|
|
• at P21 in the liver of tamoxifen-treated mice
• however, tamoxifen-treated mice subjected to left anterior descending coronary artery ligation exhibit normal macrophage numbers in the infarcted myocardium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• elevated touch withdrawal reflexes in mice injected with a cre-expressing adenovirus
• following induced spared nerve injury, mice injected with a cre-expressing adenovirus fail to exhibit detect brush even 1 week after nerve injury unlike control mice
• absence of responses to dynamic touch stimulation of hind paw in mice injected with a cre-expressing adenovirus
|
|
• following induction of inflammation induced by complete Freunds adjuvant (CFA) or capsaicin, mice injected with a cre-expressing adenovirus exhibit reduced response to brush, air puff and vibration stimuli compared with control mice
• however, response to pinch stimuli is normal
|
|
• neurons in mice injected with a cre-expressing adenovirus fail to exhibit mechanically activated currents unlike control mice
• however, Adelta and C fiber response to high-threshold mechanical stimuli is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cell-autonomous increased neurogenesis following injection of a cre-expressing adenovirus into lateral ventricles at E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• non-cell autonomous, enhanced proliferation of endothelial-derived valvar interstitial cells leading to valve thickening
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• from 6 weeks on, mice exhibit mild ear thickening unlike control mice
• tamoxifen-treated mice exhibit increased ear swelling that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
• in tamoxifen-treated mice that is not as severe as in mice with wild-type Matl1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• in the basal layer of ear skin of tamoxifen-treated mice
|
|
• reminiscent of Munros abscesses in the stratum corneum in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• from 6 weeks on, mice exhibit mild ear thickening unlike control mice
• tamoxifen-treated mice exhibit increased progressive ear swelling with ears becoming scaly and red unlike control mice
|
|
• in the ear of tamoxifen-treated mice
|
|
• in the ear of tamoxifen-treated mice
|
|
• reminiscent of Munros abscesses in the stratum corneum in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the basal layer of ear skin of tamoxifen-treated mice
|
|
• in the ear of tamoxifen-treated mice
|
|
• in the ear of tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• absence of ventral pancreato-biliary bud
|
|
• growth retardation from E9.5
• degraded posterior body trunk at E9.5
|
|
• growth retardation from E9.5
• degraded posterior body trunk at E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment at E8.5, the ventral mesencephalon is smaller and has an abnormal notch at E12.5
• depletion of TH+ neurons in the medial ventral mesencephalon and an increase in TH+ neurons in the off-midline plane in 2 of 4 embryos at E12.5
• tamoxifen treatment at E10.5 does not produce an overt phenotype in the mesencephalon
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• abrogated maturation in mice treated with tamoxifen at P5
|
|
• abrogated maturation in mice treated with tamoxifen at P5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen at E8 exhibit abnormal ventral forebrain vasculature at E12.5 compared with control mice
• tamoxifen-treated mice exhibit similar but less severe phenotypes compared with Gpr124tm1.1Vlcg homozygotes
|
|
• mice treated with tamoxifen at E8 exhibit abnormal ventral forebrain vasculature at E12.5 compared with control mice
• tamoxifen-treated mice exhibit similar but less severe phenotypes compared with Gpr124tm1.1Vlcg homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice are born and survive
|
|
• tamoxifen-treated mice are runted
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mouse embryonic fibroblasts (MEFs) from E14.5 embryos treated with 4-hydroxytamoxifen to induce deletion of the floxed Psmd11 allele exhibit increased apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment at E12.5, mice exhibit a small and partially penetrant loss of delayed non-fast spiking somatostatin/calretinin double positive cortical interneurons compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice injected with an adenovirus expressing cre recombinase (AdCre) in the ovarian bursa rapidly develop primary ovarian tumors
• treatment of isolated tumor cells with the pan-class I PI3K inhibitor, Buparlisib, results in reduced tumor cell viability
• treatment of mice with Buparlisib for 3 weeks starting at week 4 post AdCre injection extends the median latency period of ovarian tumors by 3.5 weeks
|
|
|
• ovarian tumors of intrabursally AdCre injected mice are predominately solid with some papillary areas, exhibit elongated spindle-shaped cells with vacuolated cytoplasm embedded in hyalinized matrix, appear poorly differentiated and highly disorganized, and have a hobnail appearance, indicating they resemble human ovarian clear-cell carcinoma
|
|
|
• intrabursally AdCre injected mice exhibit hemorrhagic ascites
|
|
|
• AdCre treated mice that have tumors exhibit high levels of secreted IL-6 in body fluids and ascitic fluid aspirates
|
|
|
• mice injected with an adenovirus expressing cre recombinase (AdCre) in the ovarian bursa rapidly develop primary ovarian tumors
• treatment of isolated tumor cells with the pan-class I PI3K inhibitor, Buparlisib, results in reduced tumor cell viability
• treatment of mice with Buparlisib for 3 weeks starting at week 4 post AdCre injection extends the median latency period of ovarian tumors by 3.5 weeks
|
|
|
• ovarian tumors of intrabursally AdCre injected mice are predominately solid with some papillary areas, exhibit elongated spindle-shaped cells with vacuolated cytoplasm embedded in hyalinized matrix, appear poorly differentiated and highly disorganized, and have a hobnail appearance, indicating they resemble human ovarian clear-cell carcinoma
|
|
|
• peritoneal metastases are seen in about 50% of mice injected with AdCre in the ovarian bursa
|
|
|
• mice injected with an adenovirus expressing cre recombinase (AdCre) in the ovarian bursa rapidly develop primary ovarian tumors
• treatment of isolated tumor cells with the pan-class I PI3K inhibitor, Buparlisib, results in reduced tumor cell viability
• treatment of mice with Buparlisib for 3 weeks starting at week 4 post AdCre injection extends the median latency period of ovarian tumors by 3.5 weeks
|
|
|
• ovarian tumors of intrabursally AdCre injected mice are predominately solid with some papillary areas, exhibit elongated spindle-shaped cells with vacuolated cytoplasm embedded in hyalinized matrix, appear poorly differentiated and highly disorganized, and have a hobnail appearance, indicating they resemble human ovarian clear-cell carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:219794 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 5 of 7 mice injected with an adenovirus expressing cre recombinase (AdCre) in the ovarian bursa exhibit ovarian surface epithelium hyperplasia
|
|
|
• 5 of 7 mice injected with an adenovirus expressing cre recombinase (AdCre) in the ovarian bursa exhibit ovarian surface epithelium hyperplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• heart rate is slower by 6-10% at P5 and P8
|
|
• mice are less averse to open, brightly lit spaces compared with wild-type mice
• female mice exhibit decreased anxiety-related behaviors in open field, zero-maze, and light-dark tests compared with wild-type mice
|
|
• pups are smaller than controls by 15-21% at P5 and P8
|
|
• 5HT+ axon varicosities are enlarged compared to in wild-type mice
|
|
• oxygen consumption is slightly but significantly lower at P5 and higher at P12
|
|
• autoresuscitation is less effective compared to controls following repeated episodic exposure to anoxia and results in increased mortality at P5 and P8, with only 16% of pups surviving to the endpoint at P12; deaths occur during the anoxic challenge
|
|
• tidal volume is increased by 18-34% at P8 and P12
|
|
• increase in baseline breathing variability at P5
• autoresuscitation is less effective compared to controls following repeated episodic exposure to anoxia and results in increased mortality at P5 and P8, with only 16% of pups surviving to the endpoint at P12
• pups exposed to anoxia that die at P5 take 4 times longer to initiate gasping and 4 times longer to recover heart rate and eupneic breathing to 90% of baseline
|
|
• 28% larger minute ventilation at P12
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| sudden infant death syndrome | DOID:9007 |
OMIM:272120 |
J:231745 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 8 and 11 weeks, mice exhibit increased left ventricular end-diastolic dimension compared with control mice
|
|
• at 8 and 11 weeks
|
|
• 8 week old mice show signs of dilated cardiomyopathy including left ventricle dilatation and decreased fractional shortening
|
|
• at 8 and 11 weeks, mice exhibit reduced fractional shortening compared with control mice
|
|
• 8 week old mice show signs of dilated cardiomyopathy including left ventricle dilatation and decreased fractional shortening
|
|
• at 8 and 11 weeks, mice exhibit reduced fractional shortening compared with control mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cardiomyopathy | DOID:0050700 | J:179490 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is reduced compared to mutant mice carrying Tg(MMTV-cre)4Mam
|
|
• develop a more diverse set of tumors compared to mutant mice carrying Tg(MMTV-cre)4Mam
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 42% of mice have palpable mammary tumors at the time of death
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 42% of mice have palpable mammary tumors at the time of death
|
|
• start to develop by 5 months of age in both virgin and multiparous mice
• 42% of mice have palpable mammary tumors at the time of death
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal percentages and total cell numbers of double positive or single positive thymocytes and CD4+ or CD8+ peripheral T cells in the spleen
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated and stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• systemic inflammation
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when tamoxifen is given at E13.5 or E14.5 in adult preculminate (between I-II and III) as lobules I-III are fused
|
|
• when tamoxifen is given at E10.5, at P14 lobules VI-VII occupied a greater proportion of the vermis than in wild-type
• when tamoxifen is given at E10.5, at P14 lobules VIII-IX occupied a smaller proportion of the vermis than in wild-type
• when tamoxifen is given at E13.5 or E14.5 in adult the vermis has a foliation pattern that was a milder version than that observed in tamoxifen at 10.5 mutants
• when tamoxifen is given at E13.5 or E14.5 in adult posterior region lobule VIII is shifted posterior and fused with dorsal lobule IX.
• when tamoxifen is given at E13.5 or E14.5 in adult lobules I-V and VIII/IX of the vermis were present more laterally than normal tamoxifen at E13.5 or E14.5 in adult lobules I-III were fused into one lobule
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Gli2 expression, but not Gli3 de-repression, rescues intestinal phenotypes in Smotm2Amc/Smotm2Amc Nkx3-2tm1(cre)Wez/Nkx3-2+ embryos
| N |
• mice exhibit normal intestinal development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• all mice that survive past weaning are sick by 42 days of age
|
|
|
• fewer than expected mice are found at E18.5 and at birth
|
|
|
• most survivors die before weaning
|
|
|
• live born mice develop a variety of benign and malignant tumors
• mice develop tumors in multiple organs
|
|
|
• live born mice are smaller than their control littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• all mice that survive past weaning are sick by 42 days of age
|
|
|
• fewer than expected mice are found at E18.5 and at birth
|
|
|
• most survivors die before weaning
|
|
|
• live born mice develop a variety of benign and malignant tumors
• mice develop tumors in multiple organs
|
|
|
• live born mice are smaller than their control littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• intestinal mesenchymal compartment is expanded
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• higher coronary flow after ischemia/reperfusion injury
|
|
• significantly better cardiac function after 30 minutes of ischemia followed by 30 minutes of reperfusion than in controls
• higher left ventricle developed pressure than in controls
• higher rate pressure product
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily hematopoietic tumors
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily hematopoietic tumors
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by P28
|
|
• at P17, cardiomyocytes exhibit an increase in the percentage of mononucleated and binucleated cells with a decrease in the percentage of multinucleated cells compared with control cells
• disorganized sarcomeric structure at P20
|
|
• at P20
|
|
• at P20
|
|
• increased heart weight to tibia length ratio at P20
|
|
• reduced ejection fraction and fractional shortening
|
|
• at E18.5
|
|
• increased cardiomyocytes proliferation in postnatal hearts
|
|
• at P20
|
|
• at E18.5
|
|
• at P20
|
|
• at P17, cardiomyocytes exhibit an increase in the percentage of mononucleated and binucleated cells with a decrease in the percentage of multinucleated cells compared with control cells
• disorganized sarcomeric structure at P20
|
|
• at P20
|
|
• reduced ejection fraction and fractional shortening
|
|
• at E18.5
|
|
• increased cardiomyocytes proliferation in postnatal hearts
|
|
• at P20
|
|
• at P20
|
|
• increased heart weight to tibia length ratio at P20
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no live-born mice are found indicating embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected live-born mice are found indicating embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected live-born mice are found indicating embryonic lethality
|
|
• survivors develop primarily solid tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no live-born mice are found but embryos are found at E11.5 indicating embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected live-born mice are found indicating embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 5 months after tamoxifen injections
|
|
• in tamoxifen-treated mice the walls of small arteries in the lungs, kidneys, and adrenal glands are thickened compared to oil-treated controls
• thickened vessels in the lungs show hypertrophy of the smooth muscle layers
|
|
• in tamoxifen-treated mice the walls of small arteries in the kidneys are thickened compared to oil-treated controls
|
|
• in tamoxifen-treated mice the walls of small arteries in the lungs are thickened compared to oil-treated controls
• thickened vessels in the lungs show hypertrophy of the smooth muscle layers
|
|
• seen in thickened small arteries in the lungs of tamoxifen-treated mice
|
|
• increased expression of Vwf in lung vessels of tamoxifen-treated mice suggestive of endothelial cell damage and similar to what is seen in human scleroderma patients
|
|
• in tamoxifen-treated mice the walls of small arteries in the kidneys are thickened compared to oil-treated controls
|
|
• increase in type I collagen deposition in the interstitium of tamoxifen-treated mice
|
|
• in mice, injected with tamoxifen for 5 consecutive days starting at 2 weeks of age, at 5 months of age compared to control littermates
|
|
• in tamoxifen-treated mice the walls of small arteries in the lungs are thickened compared to oil-treated controls
• thickened vessels in the lungs show hypertrophy of the smooth muscle layers
|
|
• seen in thickened small arteries in the lungs of tamoxifen-treated mice
|
|
• at 5 months after tamoxifen injections
|
|
• loss of hair on the back, head, chest, and sides and around the ears and nose in mice injected with tamoxifen for 5 consecutive days starting at 2 weeks of age
|
|
• tamoxifen-treated mice show progressive dermal fibrosis beginning by 1 month post injection
• a 2.3-fold in total collagen and disorganized collagen fibrils with increased variability in the size and shape of fibrils are seen in the skin of tamoxifen-treated mice
|
|
• dramatic increase in thickness at 5 months after tamoxifen injections
|
|
• at 5 months after tamoxifen injections
|
|
• increase in skin fragility at 5 months after tamoxifen injections
|
|
• skin feels thicker and rougher in tamoxifen treated mice compared to littermate controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic scleroderma | DOID:418 |
OMIM:181750 |
J:134135 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Failure of inner ear morphogenesis in Tbx1tm1Bld/Tbx1tm1Bld mice at E14.5 and partial rescue of inner ear morphogenesis in Tbx1tm6(cre)Bld/Tbx1tm1Bld Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/ Gt(ROSA)26Sor+ mice
| N |
• recovery of the anterior and posterior semicircular canals compared with null mice
|
|
• partial rescue with null mice
|
|
• partial rescue with null mice
|
|
• in half of mice
|
|
• in all mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Growth defects in Gt(ROSA)26Sortm1(Wnt4)Bhr/Gt(ROSA)26Sor+ Tg(Col2a1-cre)1Bhr/0 mice
|
• chondrocytes are proliferating 36% slower than controls at two weeks of age
|
|
• frontal bones are slightly smaller
|
|
• protruding incisors are observed in nine month old mice
|
|
• nasal bones of six week old mice are significantly shortened
|
|
• male mice are 50-60% of the bodyweight as age-matched controls
• female mice are 60-70% of the bodyweight as age-matched controls
|
|
• mice are undersized with shortened axial skeletons, altered head shape and disproportionately shorter limbs
|
|
• chondrocytes are proliferating 36% slower than controls at two weeks of age
|
|
• frontal bones are slightly smaller
|
|
• occipital are slightly smaller
|
|
• protruding incisors are observed in nine month old mice
|
|
• nasal bones of six week old mice are significantly shortened
|
|
• the skulls have a dome-shaped neurocranium vault
|
|
• the pubic and ischial bones have failed to fuse at six weeks of age
• ossification of the bones occurs by 8 weeks of age but the pubic bone is still thinner
|
|
• vertebrae are narrow and flat caused by a reduction in lateral bone
|
|
• axial skeletion is shortened compared to wild-type controls
|
|
• the tibiae are deficient in bone marrow and are instead filled with adipocytes at 9 months of age
|
|
• found in mice two weeks of age
|
|
• found in mice two weeks of age with less columnar organization
|
|
• less vascular endothelium growth factor is expressed by cells in the chondrocyte zones of the tibiae
|
|
• primary ossification centers do not form in the tibiae until after E15.5
• formation of secondary ossification centers in the tibiae are delayed by four days
|
|
• frontal bones are slightly smaller
|
|
• occipital are slightly smaller
|
|
• protruding incisors are observed in nine month old mice
|
|
• nasal bones of six week old mice are significantly shortened
|
|
• the skulls have a dome-shaped neurocranium vault
|
|
• visibly shorter
|
|
• slow movement, which is possibly a result of the abnormal skeletal features
|
|
• nasal bones of six week old mice are significantly shortened
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no live-born mice are found indicating embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop both solid and hematopoietic tumors with many mice having both types of tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily solid tumors
|
|
• develop various carcinomas with poor differentiation and metastasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily solid tumors
|
|
• develop various carcinomas with poor differentiation and metastasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily hematopoietic tumors
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop primarily hematopoietic tumors
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
• most mice develop aggressive leukemias and lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with diphtheria toxin, light pupilary reflex is lost
|
|
• following treatment with diphtheria toxin, 90% of melanopsin retinal ganglion cells are ablated
|
|
• following treatment with diphtheria toxin, projections into the suprachiasmatic nucleus are reduced compared to in wild-type mice
|
|
• following treatment with diphtheria toxin, 90% of melanopsin retinal ganglion cells are ablated
|
| N |
• despite ablation of melanopsin retinal ganglion cells following treatment with diphtheria toxin, mice exhibit normal image-forming visual responses
|
|
• following treatment with diphtheria toxin, light pupilary reflex is lost
|
|
• following treatment with diphtheria toxin, mice lose their ability to photo-entrain their circadian rhythm and mice maintain equal activity during light and dark phases unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the apical region of the cochlea aberrant axonal projections that cross, loop, and extend beyond the epithelium are seen
• at P1 total area of the spiral ganglion is reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• E11.5 neural precursor cells cultured for 9 days in the presence of S33Y beta-catenin and tamoxifen exhibit enhanced neuronal differentiation compared with similarly treated control Rnf2tm1Mvi cells
• E17.5 neural precursor cells cultured for 3 days in the presence of S33Y beta-catenin and tamoxifen exhibit enhanced neuronal differentiation compared with similarly treated control Rnf2tm1Mvi cells
• neuronal precursor cells treated with tamoxifen and subjected to growth factor deprivation at the late stage (12 days in culture) exhibit reduced astrocyte differentiation compared with similarly treated control Rnf2tm1Mvi cells
• at P2.5, tamoxifen-treated mice exhibit reduced astrocytic differentiation compared with similarly treated control Rnf2tm1Mvi cells
|
|
• E11.5 neural precursor cells cultured for 9 days in the presence of S33Y beta-catenin and tamoxifen exhibit enhanced neuronal differentiation compared with similarly treated control Rnf2tm1Mvi cells
• E17.5 neural precursor cells cultured for 3 days in the presence of S33Y beta-catenin and tamoxifen exhibit enhanced neuronal differentiation compared with similarly treated control Rnf2tm1Mvi cells
• neuronal precursor cells treated with tamoxifen and subjected to growth factor deprivation at the late stage (12 days in culture) exhibit reduced astrocyte differentiation compared with similarly treated control Rnf2tm1Mvi cells
• at P2.5, tamoxifen-treated mice exhibit reduced astrocytic differentiation compared with similarly treated control Rnf2tm1Mvi cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice develop kindey cysts
• however, treatment with Genz-123346 inhibits cystogenesis
|
|
• tamoxifen-treated mice exhibit progressive renal function decline over 4 to 5 weeks
• however, treament with Genz-123346 improves kidney fucntion
|
|
• tamoxifen treated mice develop kindey cysts
• however, treatment with Genz-123346 inhibits cystogenesis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:162080 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen-treatment, mouse embryonic fibroblasts (MEFs) exhibit random migration in response to an HMGB1 gradient unlike wild-type cells
|
|
• 180 minutes after exposure to HMGB1, tamoxifen-treated MEFs exhibit reduced migration velocity compared with wild-type mice
|
|
• following tamoxifen-treatment, MEFs exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells that is not rescued by Nfkb2
• however, chemotaxis in response to PDGF is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• lineage-tracing analysis showed no apparent defects in cranial, cardiac and enteric neural crest cell migration
|
| N |
• lineage-tracing analysis showed no apparent defects in cranial, cardiac and enteric neural crest cell migration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit beta to alpha cell transdifferentiation
|
|
• mice exhibit beta to alpha cell transdifferentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at E10.5, E14.5 and E18.5, cardiac neural crest cell development is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Cardiovascular abnormalities in Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+ Tg(Smad7-cre)1Sjc/0 embryos
|
• cardiovascular developmental abnormalities result in in utero death
|
|
• yolk sacs of mutant embryos have almost no vasculature compared to controls
|
|
• observed in E10.5 embryos
|
| N |
• in mutants, ventricular myocardium and endothelial layer are intact
|
|
• vessels are weakened and hemorrhagic in embryos
|
|
• dorsal aorta is fragmented and contains only a few smooth muscle cells
|
|
• yolk sacs of mutant embryos have almost no vasculature compared to controls
|
|
• atrioventricular (AV) cushion region is largely absent in mutants
|
|
• cushion hypoplasia is observed at E10
|
|
• E10.5 embryos have smaller hearts relative to controls
|
|
• E10.5 embryos are hemorrhagic
|
|
• observed in E10.5 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a decrease in the CD71- Ter119+ population, an intermediate erythroid progenitor stage in the bone marrow
|
|
• 50 days after tamoxifen induction with a subcutaneous pellet
|
|
• 50 days after tamoxifen induction with a subcutaneous pellet
|
|
• 50 days after tamoxifen induction with a subcutaneous pellet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following exposure to tamoxifen, neuronal differentiation in culture induced by FGF2 deprivation or S33Y beta-catenin expression is enhanced compared to in similarly treated control mice
• following exposure to tamoxifen, the reduction in Ngn1+ cells in the late neurogenic phase (E17.5) is suppressed compared to in similarly treated control mice
|
|
• following exposure to tamoxifen, neuronal differentiation in culture induced by FGF2 deprivation or S33Y beta-catenin expression is enhanced compared to in similarly treated control mice
• following exposure to tamoxifen, the reduction in Ngn1+ cells in the late neurogenic phase (E17.5) is suppressed compared to in similarly treated control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• approximately 20% of mice die suddenly with no ante-mortem indication of illness within 60 days after high dose tamoxifen treatment
|
|
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
|
|
• tamoxifen induced ablation of sinoatrial node cells is accompanied by a destructive fibrosis of nodal tissue
|
|
• following 5 days of tamoxifen treatment show alternating periods of slow and fast frequencies in R-R tachograms
• alterations of long electrical standstills (sinus pauses) and intermittent rapid atrial activity following tamoxifen treatment
• following 5 days of tamoxifen treatment absolute value of the maximally (isoprenaline) stimulated heart rate remained low
|
|
• following 5 days of high or low dose tamoxifen treatment heart rate falls by about 40 - 50% or 12%, respectively
|
|
• variety of cardiac rhythm disturbances; including sino-atrial arrhythmia, sino-atrial pause and to a minor extent supraventricular or ventricular tachycardia, following tamoxifen treatment
|
|
• complete heart block some weeks after tamoxifen treatment
|
|
• following tamoxifen treatment
• progressive prolongation of the P-R interval tends to result in complete isolated contraction of atria and ventricles with high dose tamoxifen treatment
|
|
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| sick sinus syndrome | DOID:13884 |
OMIM:163800 OMIM:608567 |
J:186021 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the spleen and bone marrow B cell subsets of tamoxifen-treated mice
|
|
• tamoxifen-treated B cell precursors fail to exhibit an increase in bafilomycin-induced autophagy unlike in control cells
|
|
• in the spleen and bone marrow B cell subsets of tamoxifen-treated mice
|
|
• tamoxifen-treated B cell precursors fail to exhibit an increase in bafilomycin-induced autophagy unlike in control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 embryos are found at later stages, after expected midgestation lethality from cardiovascular failure
|
|
• mice display moderate splenic enlargement and partial rescue of splenic architecture
• germinal centers are present
• splenic fibrosis is not observed
|
|
• mice display moderate splenic enlargement and partial rescue of splenic architecture
• germinal centers are present
• splenic fibrosis is not observed
|
|
• marked enlargement of dorsal root ganglia and other neural crest derived tissues is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• failure to repair DNA-protein crosslinks (DPCs) in mouse embryo fibroblasts (MEFs)
• increased accumulation of camptothecin (CPT)-induced topoisomerase 1 cleavage complex (Top1cc) foci in MEFs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• specification of the definitive endoderm is disrupted
|
|
• visceral endoderm fails to displace proximally at E7.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• embryos are obtained unlike in triple mutants that are heterozygous for the Dph1 allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• embryos retain their heads and appear normal at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in some mice 7 months after tamoxifen treatment
|
|
• 7 months after tamoxifen treatment
|
|
• 7 months after tamoxifen treatment
|
|
• in some mice 7 months after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• anterior to posterior cell fate transformation is detected at 10 days post coitum, resulting in anterior forebrain reduction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• anterior to posterior cell fate transformation is detected at 10 days post coitum, resulting in anterior forebrain reduction
• alterations are more severe than observed in corresponding Hesx1tm2Jpmb compound mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• electrical stimulation of spinal cords to induce locomotor activity is decreased by about 25% when Shox2 interneurons are inactivated by light, which is similar to the phenotype observed when the population of Shox2 interneurons is ablated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly disturbed after 3 days of tamoxifen treatment (which results in loss of more than 50% of insterstitial cells of Cajal (ICCs)
|
|
• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity
|
|
• total GI transit time is increased to more than 5 hours; similar transit time is measured in tamoxifen-treated mutants that have been repopulated with wild-type mast cells (by adaptive BM transplant)
|
|
• tamoxifen-treated mice have delayed gastric emptying
|
|
• in tamoxifen treated mice, excitatory enteric neurotransmission is blocked as result of ICC depletion
|
|
• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• some mice (5/208) survive to birth while all Nf1-null homozygotes expressing either Gt(ROSA)26Sortm1Fia or Hprt1tm1(CMV-cre)Brd die prior to birth
|
|
|
• massively enlarged
|
|
|
• peripheral ganglia are massively enlarged in newborns
|
|
|
• enormous paraspinal masses arise from the dorsal root ganglia
|
|
|
• medulla is overgrown compared with wild-type, with cortical effacement and tumor-like medullary protrusion
|
|
|
• elevate Ras levels return to wild-type levels by E12.5 with expression of Gt(ROSA)26Sortm1Fia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal invariant NKT cell numbers, phenotype and in vivo responsiveness to lipid antigens
|
|
• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells
• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells
• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells
• however, iNKT cells exhibit normal trafficking to the tumor site
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells
• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells
• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells
• however, iNKT cells exhibit normal trafficking to the tumor site
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to disease at 12-16 weeks of age
|
|
• marker analysis indicates impaired keratinocyte differentiation
|
|
• mice develop mild skin dermatitis
|
|
• mice develop mild skin dermatitis
|
|
• marker analysis indicates impaired keratinocyte differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated lung mesenchymal fibroblasts cocultured with isolated SFTPC+ distal alveolar stem cells results in reduced distal alveolar organoid growth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• tamoxifen-treated mice exhibit normal invariant NKT cell numbers, phenotype and in vivo responsiveness to lipid antigens
|
|
|
• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells
• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells
• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells
• however, iNKT cells exhibit normal trafficking to the tumor site
|
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
|
• from iNKT cells from tamoxifen-treated mice in response to EL4 targets
|
|
|
• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells
• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells
• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells
• however, iNKT cells exhibit normal trafficking to the tumor site
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen-treatment, mouse embryonic fibroblasts (MEFs) exhibit random migration in response to an HMGB1 gradient unlike wild-type cells
|
|
• 30 to 60 minutes after exposure to HMGB1, tamoxifen-treated MEFs exhibit reduced migration velocity compared with wild-type mice
|
|
• following tamoxifen-treatment, MEFs exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis in response to PDGF is normal and chemotaxis is rescued by over expression of Nfkb2
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• total bone marrow cells transplanted in lethally irradiated recipients and treated with tamoxifen induce aggressive T-cell acute lymphoblastic leukemia (T-ALL) resulting in death unlike control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• total bone marrow cells transplanted in lethally irradiated recipients and treated with tamoxifen induce a low abundant transient wave of CD4/CD8 double-positive T cells without inducing acute T cell leukemia (T-ALL) compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups lose the righting reflex between 5-12 weeks of age
|
|
• pups develop spontaneous seizures characterized by periods of wild and uncontrolled running by 12 weeks of age
|
|
• swollen subiliac lymph nodes
|
|
• P10 pups exhibit mild alopecia by 3 weeks, progressing to severe alopecia by 12 weeks of age
|
|
• pups exhibit delayed fur growth at P10
|
|
• pups develop spontaneous seizures characterized by periods of wild and uncontrolled running by 12 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced immunohistochemistry at E15.5 in the pancreas
|
|
• reduced immunohistochemistry at E15.5 in the pancreas
|
|
• reduced immunohistochemistry at E15.5 in the pancreas
|
|
• reduced immunohistochemistry at E15.5 in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite loss of retinal pigment epithelia in tamoxifen treated mice, the retinal pigment epithelial barrier function is maintained and retinal vasculature is normal
|
|
• loss of retinal pigment epithelium in tamoxifen treated mice is compensated by increased size of neighboring cells without loss of cell thickness preventing gaps in the epithelium
|
|
• 6 days after tamoxifen treatment, retinal pigment cells become round and are exuded from the retina
• 2 weeks after tamoxifen treatment, retinal pigment cells are enlarged and irregularly shaped with clumps of extruding cells
• 14 days after tamoxifen treatment the retinal pigment cells are reduced 68% compared to in mice lacking the cre transgene
• however, loss of retinal pigment cells is stabilized between day 14 and 6 months
|
|
• following tamoxifen treatment, mice develop variable retinal folds termed rossetting unlike wild-type mice
|
|
• under scotopic conditions at 6 weeks and 6 months, tamoxifen-treated mice exhibit decreased a and b wave amplitudes compared with wild-type mice
|
|
• loss of retinal pigment epithelium in tamoxifen treated mice is compensated by increased size of neighboring cells without loss of cell thickness preventing gaps in the epithelium
|
|
• 6 days after tamoxifen treatment, retinal pigment cells become round and are exuded from the retina
• 2 weeks after tamoxifen treatment, retinal pigment cells are enlarged and irregularly shaped with clumps of extruding cells
• 14 days after tamoxifen treatment the retinal pigment cells are reduced 68% compared to in mice lacking the cre transgene
• however, loss of retinal pigment cells is stabilized between day 14 and 6 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 50% of mice die 52 weeks after tamoxifen injection
|
|
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection
|
|
• all recovered tamoxifen-treated mice develop secondary, late-onset neurological symptoms and demyelinating disease starting around 40 weeks after injection
• mice injected with MOG(35-55)-coupled polylactic-co-glycolic acid nanoparticles 32 weeks after tamoxifen injection show inhibition of disease progression
• mice exhibit rare focal lesions in the brainstem, cerebellum, and spinal cord at 40 weeks after tamoxifen injection
• at 1 year after tamoxifen injection, focal lesions in these regions are no longer seen
|
|
• tamoxifen treated mice exhibit loss of oligodendrocytes, peaking 5 weeks after injection and recovering by 10 weeks
• brainstem shows an approximate 50% decrease in oligodendrocytes at 1 year after tamoxifen treatment
• however, substantial oligodendrocyte loss in other CNS areas is not seen at 1 year after tamoxifen treatment
|
|
• white matter lesions in tamoxifen injected mice show presence of macrophages containing myelin debris and unmyelinated axons, indicating ongoing demyelination
|
|
• thinner myelin in both tamoxifen treated and untreated mice (due to leakiness of the cre-expressing transgene)
|
|
• axonal loss in the ventrolateral white matter of the cervical spinal cord (40%) and the optic nerve (55%) at 1 year after tamoxifen treatment
|
|
• tamoxifen treated mice exhibit widespread CNS demyelination, peaking 5 weeks after injection and recovering by 10 weeks
• mice exhibit widespread myelin loss at 1 year after tamoxifen injection
• mice not treated with tamoxifen show some myelin loss in most CNS areas at 52 weeks of age, indicating leakiness of the cre-expressing transgene
• untreated mice exhibit about 30% fewer unmyelinated axons in the corpus callosum compared to tamoxifen treated mice
|
|
• mice show impaired motor skills starting around 40 weeks after tamoxifen injection
|
|
• tamoxifen treated mice exhibit severe ataxia starting around 40 weeks after injection
|
|
• mice show weight loss starting around 40 weeks after tamoxifen injection
|
|
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection
|
|
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection
|
|
• total numbers of CD4+ T cells, CD8+ T cells, B cells, monocytes, and dendritic cells in the CNS-draining cervical lymph nodes of tamoxifen treated mice is higher than in controls
|
|
• at 40 weeks after tamoxifen injection, autoreactive T cells capable of proliferating in response to stimulation with recombinant MOG protein are seen in the spleen and cervical lymph nodes indicating an adaptive autoimmune response against myelin
|
|
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection
|
|
• tamoxifen treated mice exhibit loss of oligodendrocytes, peaking 5 weeks after injection and recovering by 10 weeks
• brainstem shows an approximate 50% decrease in oligodendrocytes at 1 year after tamoxifen treatment
• however, substantial oligodendrocyte loss in other CNS areas is not seen at 1 year after tamoxifen treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:234435 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice are sacrificed within a few weeks of birth with respiratory distress
|
|
• in mice surviving to 15 weeks
|
|
• in mice surviving to 15 weeks
|
|
• in mice surviving to 15 weeks
|
|
• in mice surviving to 15 weeks
|
|
• mice that survive to 15 weeks exhibit hyperplasia of the lung epithelium in the bronchi, bronchioles, and alveoli unlike wild-type mice
|
|
• within a few weeks of birth
|
|
• in mice surviving to 15 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal locomotor activity under normal conditions
|
|
• mice exhibit attenuated methamphetamine-induced hyperlocomotion compared with control mice
|
| N |
• normal brain weight
|
| N |
• normal body weight
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice surviving to weaning age are reduced in number when compared to expected numbers
|
|
• all mutants surviving to weaninig age display eye defects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10% of embryos exhibit exencephaly
• Background Sensitivity: phenotype is background-dependent, as mutants on C57BL/6J;CD-1 background do not display exencephaly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reactivation is prevented after in vitro activation with Ova and tamoxifen treatment
|
|
• reactivation is prevented after in vitro activation with Ova and tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die shortly after birth
|
|
• multiple
|
|
• at E14.5, kidneys exhibit a thin cortical nephrogenic zone and poor nephron development
• mice exhibit depletion of nephron progenitors and premature tubule formation
• at E12.5, ectopic tubules are observed dorsal to the poorly branched ureteric bud-derived epithelia
|
|
• at E14.5, kidneys lack condensed metanephric mesenchyme around the ureteric buds in the cortex and contain few Pax2+ scattered tubules
|
|
• at E14.5, no ureteric bud-derived epithelia are observed in the mutant cortex
|
|
• thin cortical nephrogenic zone at E14.5
|
|
• at E14.5
• severe at birth
|
|
• some of the dilated tubules are positive for a proximal tubule marker
• however, proximal tubules are not overproduced
|
|
• at E14.5, ureteric bud branching is impaired
|
|
• multiple
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only a minority of dopaminergic projections remain intake
|
|
• YFP+ dopamine neurons fail to exhibit glutamatergic excitatory postsynaptic currents (EPSCs) unlike control cells
• at P9 to P10, mice exhibit a reduction in glutamatergic with fewer neurons responding to ventral tegmental area stimulation compared with similarly treated control cells
|
|
• cocaine-treated mice exhibit less locomotor activity compared with control mice
• however, cocaine-treated mice exhibit conditioned place preference
|
|
• the ventral striatum exhibit reduced dopamine and evoked dopamine release compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following tamoxifen treatment, mice display normal alveolar spaces and normal lung structure with no detectable mucosal cells
• expression of key lung molecular markers remains normal in adult lungs
|
|
|
• following tamoxifen treatment, mice display uterine hyperplasia
|
|
• following tamoxifen treatment, mice display dermal papillomas
|
|
• following tamoxifen treatment, mice display dermal papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit smaller hearts than mice homozygous for null alleles of Fgfr1 and Fgfr2 due to decreased myocardial proliferation
• however, coronary development is normal
|
|
• mice exhibit thinner ventricular walls than mice homozygous for null alleles of Fgfr1 and Fgfr2
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 85 days following injection of PDGF and cre compared with 27 days for similarly treated Ptentm1Hwu Trp53tm1Thl double homozygotes
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glioblastoma proneural subtype | DOID:0050804 | J:172585 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit small hearts due to decreased myocardial proliferation
• however, coronary development is normal
|
|
• the ventricular wall thickness is 67+/-8% of wild-type but not as thin as in homozygotes (54+/-6%)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 27 days following injection of PDGF and cre compared with 85 days for similarly treated Ptentm1Hwu homozygotes
|
|
• following injection of PDGF and cre, tumor growth is increased compared to in similarly treated Ptentm1Hwu homozygotes
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
|
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glioblastoma proneural subtype | DOID:0050804 | J:172585 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the superficial dorsal horn, there are significantly fewer ( about 50%) lacZ-marked neurons compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• as early as 4 days after tamoxifen-induction
|
|
|
• following tamoxifen treatment, the number of hematopoietic stem cell-containing LSK populations is decreased compared to in similarly treated wild-type mice
|
|
|
• following tamoxifen treatment, maintenance of adult hematopoietic cells is abolished compared to in similarly treated wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in culture following treatment with tamoxifen regardless of activation status T cell survival is decreased comapred to similarly treated wild-type cells
|
|
• in culture following treatment with tamoxifen regardless of activation status T cell survival is decreased comapred to similarly treated wild-type cells
|
|
• in culture following treatment with tamoxifen regardless of activation status T cell survival is decreased comapred to similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• quantification of neurons at P0 shows a 50% decrease in number of marked neurons in superficial dorsal horn compared to controls with no difference in numbers in any other spinal cord region
• significant increase in number of apoptotic cells (marked neurons) in superficial dorsal horn is observed at E18.5, but no difference is observed at E17.5 or 19.5
• partial loss of glutamatergic and GABAergic neurons is observed in dorsal horn
• number of marked neurons in dorsal horn are not different from controls when BrdU labeling is done at E12.5 or E13.5 and analysis is done at E17.5, indicating that neuronal mitosis is not affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following injection of PDGF and cre, mice do not develop tumor-related morbidity
|
| N |
• following injection of PDGF and cre, mice do not develop tumor-related morbidity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice do not live beyond 2 weeks of age due to intestinal failure
|
|
• intestinal defects are seen by day 9 of tamoxifen treatment
• die of intestinal failure
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice do not live beyond 2 weeks of age due to intestinal failure
|
|
• intestinal defects are seen by day 9 of tamoxifen treatment
• die of intestinal failure
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the interfrontal bone is noticeably larger than controls starting at E16.5
• newborns have an overgrowth of the interfrontal bone in the anterior frontal calvaria
• the frontal bones of five day old mice are structured more trabecularly and have an increased portion of calcified bone matrix
|
|
• three-fold more osteprogenitors are actively proliferating within the frontal sutures of E19.5 fetuses compared to controls
• 1.4 fold more primary osteoblasts of calvaria tissue actively proliferate in vitro compared to controls
|
|
• all osteprogenitors from interfrontal bones differentiate into osteoblasts after three days in culture compared to only half of controls
|
|
• coronal suture closing begins 15 days after birth and is completed by 20 days of age
|
|
• premature fusion of the posterior frontal suture is seen at 5 days after birth
• by 10 days after birth, fusion of the anterior frontal suture becomes evident
|
|
• the interfrontal bone is noticeably larger than controls starting at E16.5
• newborns have an overgrowth of the interfrontal bone in the anterior frontal calvaria
• the frontal bones of five day old mice are structured more trabecularly and have an increased portion of calcified bone matrix
|
|
• a shortened craniofacial area is noticeable at one week after birth and worsens as the mice age
|
|
• the interfrontal bone is noticeably larger than controls starting at E16.5
• newborns have an overgrowth of the interfrontal bone in the anterior frontal calvaria
• the frontal bones of five day old mice are structured more trabecularly and have an increased portion of calcified bone matrix
|
|
• a shortened craniofacial area is noticeable at one week after birth and worsens as the mice age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit an increase in blood vessel density in the skin compared with wild-type mice
• hair follicles are surrounded by lymphatic or blood vessels unlike in wild-type mice
|
|
• mice exhibit an increase in lymphatic and blood vessel density in the skin compared with wild-type mice
|
|
• transplanted MCF-7 tumor cells exhibit increased lymphangiogenesis compared to when transplanted into wild-type mice
|
|
• mice exhibit increased in vitro and in vivo lymphatic permeability associated with disorganized lymphatic cell-cell junctions compared to in wild-type mice
|
|
• transplanted MCF-7 tumor cells exhibit increased lymphangiogenesis compared to when transplanted into wild-type mice
|
|
• mice exhibit increased metastasis of transplanted mammary cancer cell (line 66c14) compared with similarly treated wild-type mice
|
|
• mice exhibit increased in vitro and in vivo lymphatic permeability associated with disorganized lymphatic cell-cell junctions compared to in wild-type mice
|
|
• mice transplanted with human breast carcinoma MCF-7 cells exhibit increased lymphangiogenesis compared with similarly treated wild-type mice
|
|
• mice exhibit an increase in lymphatic vessel density in the skin compared with wild-type mice
• hair follicles are surrounded by lymphatic or blood vessels unlike in wild-type mice
|
|
• mice exhibit an increase in lymphatic and blood vessel density in the skin compared with wild-type mice
|
|
• poorly developed
|
|
• hair follicles are surrounded by lymphatic or blood vessels unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
|
|
• enlarged following doxycycline treatment at E12.5
|
|
• reduced or absent following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
|
|
• reduced following doxycycline treatment at E13.5
|
|
• following doxycycline treatment at E12.5, E11.5 or at E10.5
|
|
• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
|
|
• following doxycycline treatment at E10.5
|
|
• following doxycycline treatment at E12.5 in some mice
|
|
• following doxycycline treatment at E10.5, E12.5, or E13.5
|
|
• shortened face following doxycycline treatment at E10.5
|
|
• following doxycycline treatment at E12.5
|
|
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
|
|
• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
|
|
• following doxycycline treatment at E10.5 the orientation of the eyes is more anterior
|
|
• following doxycycline treatment at E12.5 in some mice
|
|
• following doxycycline treatment at E10.5, E12.5, or E13.5
|
|
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
|
|
• following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
|
|
• enlarged following doxycycline treatment at E12.5
|
|
• reduced or absent following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
|
|
• reduced following doxycycline treatment at E13.5
|
|
• following doxycycline treatment at E12.5, E11.5 or at E10.5
|
|
• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
|
|
• following doxycycline treatment at E10.5
|
|
• following doxycycline treatment at E12.5 in some mice
|
|
• following doxycycline treatment at E10.5, E12.5, or E13.5
|
|
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
|
|
• reduced or absent following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• following doxycycline treatment at E12.5
|
|
• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
|
|
• reduced following doxycycline treatment at E13.5
|
|
• following doxycycline treatment at E12.5, E11.5 or at E10.5
|
|
• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
|
|
• following doxycycline treatment at E10.5
|
|
• following doxycycline treatment at E12.5 in some mice
|
|
• following doxycycline treatment at E10.5, E12.5, or E13.5
|
|
• shortened face following doxycycline treatment at E10.5
|
|
• following doxycycline treatment at E12.5
|
|
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
|
|
• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice administered doxycycline in the diet develop melanoma with a median latency of 60 days and with 85% penetrance
• withdrawal of doxycycline leads to rapid tumor regression
• treatment with PLX4720 BRAF inhibitor results in tumor growth inhibition in mutants, however, after continual administration of this inhibitor, mice develop drug resistance
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• renal hypoplasia with a 50-80% reduction in branch numbers at E14
|
|
• 50-80% reduction in branch numbers at E14
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10% to 15% at E18.5
|
|
• as determined by marker expression, cartilage growth in long bones is reduced due to premature onset of hypertrophy compared with wild-type mice
|
|
• decreased at E14.5 and E18.5
|
|
• at E18.5
|
|
• at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike Runx2tm1Mjo homozygotes, mice exhibit normal bone collar
|
|
• like Runx2tm1Mjo homozygotes, mice lack a marrow cavity
|
|
• at E18.5, bone formation defects observed in Runx2tm1Mjo homozygotes are partially recovered in the endochondrial skeleton but not the skull
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• alveolar stem cell renewal is disrupted, with tamoxifen-treated mice showing reduced fractions of SFTPC+ alveolar stem cells that incorporate BrdU during normal homeostasis and during injury with bleomycin
|
|
• tamoxifen-treated mice show reduced density of alveoli in the distal lung
• tamoxifen-treated mice exhibit a more simplified alveolar structure in which secondary crests are absent from the enlarged alveoli
|
|
• tamoxifen-treated mice show a loss of SFTPC+ type 2 pneumocytes from the distal alveolar region
|
|
• tamoxifen-treated mice show enlarged alveolus size
|
|
• tamoxifen-treated mice exhibit emphysematous changes in the alveolar airspace characterized by a 20% enlargement of airspace, increase in mean chord length, enlarged alveolus size, and reduced density of alveoli in the distal lung
• lungs of tamoxifen-treated mice show elevated low attenuation volume/total lung volume ratio, indicating airspace enlargement and emphysema
• however, no evidence of increased inflammatory cells or increased in the number of apoptotic cells in the lungs of tamoxifen-treated mice are seen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pulmonary emphysema | DOID:9675 |
OMIM:130700 |
J:264185 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 97% of B lineage cells are EYFP-positive compared with 33% in Cd19tm1(cre)Cgn-expressing mice indicating more efficient loxP recombination in developing B cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• alpha cells in diphtheria-treated mice transdifferentiate into beta cells
|
|
|
• alpha cells in diphtheria-treated mice transdifferentiate into beta cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups injected with tamoxifen at P1-P3 show a decreased density of the vessel network covering a smaller area of the retina at P6; the vascular density and number of branching points are significantly lower in the periphery and center of P6 retinas
• however, mice injected with tamoxifen at an adult stage show no alterations in the number of branching points and vascular density in adult retinas
|
|
• pups injected with tamoxifen at P1-P3 show a small but significant reduction in the number of tip cells per vessel length and abnormal pericyte morphology resulting in decreased pericyte coverage of blood vessels in P6 retinas
• however, the number of filopodia per tip cell is relatively normal at P6
|
|
• pups injected with tamoxifen at P1-P3 show abnormal pericyte morphology, with mural cells "bulging out" from blood vessels, in P6 retinas
|
|
• pups injected with tamoxifen at P1-P3 show a decreased density of the vessel network covering a smaller area of the retina at P6; the vascular density and number of branching points are significantly lower in the periphery and center of P6 retinas
• however, mice injected with tamoxifen at an adult stage show no alterations in the number of branching points and vascular density in adult retinas
|
|
• pups injected with tamoxifen at P1-P3 show a small but significant reduction in the number of tip cells per vessel length and abnormal pericyte morphology resulting in decreased pericyte coverage of blood vessels in P6 retinas
• however, the number of filopodia per tip cell is relatively normal at P6
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop a wasting syndrome and succumb to disease by 11 weeks of age
|
|
• mice develop an enlarged spleen
|
|
• loss of hypodermal fat
|
|
• marker analysis indicates impaired keratinocyte differentiation
|
|
• mice with advanced disease show loss of skin barrier integrity at 7-8 weeks of age
|
|
• mice develop severe, systemic dermatitis starting at 5 weeks of age
• inflammation is not seen in the lung, liver, kidney or gut
|
|
• dermatitis is accompanied by hair loss
|
|
• loss of hair follicles
|
|
• mild epidermal hyperplasia and microabsceess are seen at 3 weeks of age but not at 10 days of age
|
|
• skin contains epidermal scales
|
|
• skin of mice with advanced disease contains lesions with epidermal damage, resulting in loss of skin barrier integrity
|
|
• dermatitis is accompanied by skin thickening
|
|
• increase in dermal fibrosis
|
|
• mice develop an enlarged spleen
|
|
• decrease in the frequency of Foxp3+ CD25+ Tregs with a corresponding increase in Foxp3-CD25+ effector T cells
|
|
• CD4 T cells exhibit an activated phenotype
• mice develop systemic T helper type 2 immunity
|
|
• mice develop peripheral lymphadenopathy
|
|
• mice develop severe, systemic dermatitis starting at 5 weeks of age
• inflammation is not seen in the lung, liver, kidney or gut
|
|
• mice with advanced disease show loss of skin barrier integrity at 7-8 weeks of age
|
|
• mice develop an enlarged spleen
|
|
• decrease in the frequency of Foxp3+ CD25+ Tregs with a corresponding increase in Foxp3-CD25+ effector T cells
|
|
• CD4 T cells exhibit an activated phenotype
• mice develop systemic T helper type 2 immunity
|
|
• marker analysis indicates impaired keratinocyte differentiation
|
|
• loss of hypodermal fat
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• apoptotic cells in the nephron as early as P7
|
|
• apoptotic cells in the nephron as early as P7
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• spared beta cells in diphtheria- and tamoxifen-treated mice do not exhibit increased replication
|
|
|
• bihormonal (glucagon+ and insulin+) cells arise in the islets of diphtheria-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following pIpC induction cultured precursor cells fail to produce plasmacytoid dendritic cells
|
|
• following pIpC induction cultured precursor cells fail to produce plasmacytoid dendritic cells
|
|
• mild decrease in the total number of cells in GM-CSF-supplemented cultures following pIpC treatment
|
|
• following pIpC induction cultured precursor cells fail to produce plasmacytoid dendritic cells and in vivo
|
|
• in Flt3L-supplemented cultures following pIpC induced deletion in hematopoietic stem cells and in vivo
|
|
• following pIpC induction cultured precursor cells fail to produce plasmacytoid dendritic cells
|
|
• mild decrease in the total number of cells in GM-CSF-supplemented cultures following pIpC treatment
|
|
• following pIpC induction cultured precursor cells fail to produce plasmacytoid dendritic cells and in vivo
|
|
• in Flt3L-supplemented cultures following pIpC induced deletion in hematopoietic stem cells and in vivo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal appendage development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• when the Wnt1:GFP fusion protein is expressed in the Wolffian duct, embryos exhibit normal mesonephric and metanephric tubule induction, as well as caudal extension of the Mullerian duct
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• euthanized 12 weeks after tamoxifen-treatment
|
|
• in tamoxifen-treated mice, particularly evident on the abdominal skin
|
|
• tamoxifen-treated mice develop more severe epidermal disease (thick skin, hair loss and scaling) compared with control mice
|
|
• 3.5-fold in tamoxifen-treated mice than in control mice
|
|
• in tamoxifen-treated mice, particularly evident on the abdominal skin
|
|
• in tamoxifen-treated mice
|
|
• accelerated neoplasm development in tamoxifen-treated mice compared with control mice
|
|
• accelerated neoplasm development in tamoxifen-treated mice compared with control mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following reactivation
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• peripheral T cells are reduced compared to in wild-type mice
• in transplantation experiments, T cells are less competitive than wild-type T cells
|
|
• in the thymus
|
|
• in the thymus
|
|
• CD4+ thymocytes are more profoundly decreased than CD8+ thymocytes
|
|
• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
• YFP+ T regulatory cells exhibit reduced ability to suppress naive T cell proliferation compared with wild-type T cells
|
|
• following anti-CD3/anti-CD28 stimulation, slightly fewer IFN-gamma producing single positive T cells are detected compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
|
|
• following anti-CD3/anti-CD28 stimulation, IL2 production by single positive T cells is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
|
|
• mice exhibit dermatitis unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• mice weight less than wild-type mice
• however, transfer of regulatory T cells restores normal weight gain
|
|
• mice exhibit rectal prolapse unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• following reactivation
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• peripheral T cells are reduced compared to in wild-type mice
• in transplantation experiments, T cells are less competitive than wild-type T cells
|
|
• in the thymus
|
|
• in the thymus
|
|
• CD4+ thymocytes are more profoundly decreased than CD8+ thymocytes
|
|
• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
• YFP+ T regulatory cells exhibit reduced ability to suppress naive T cell proliferation compared with wild-type T cells
|
|
• mice exhibit dermatitis unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• mice exhibit alopecia unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• following reactivation
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• half of mice die at E11.5
|
|
• the number of cardiac neural crest cells is increased in the cardiac jelly compared to in wild-type mice
|
|
• the number of cardiac neural crest cells is increased in the cardiac jelly compared to in wild-type mice
|
|
• at E11.5, surviving mice exhibit a lack of cushions in the distal outflow tract while more proximal outflow tract cushions are closer to each other unlike in wild-type mice
|
|
• at E15.5
|
|
• the number of cardiac neural crest cells is increased in the cardiac jelly compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice infected with Citrobacter exhibit increased transient weight loss compared with wild-type mice and mice heterozygous for a knock-out allele
• however, mice exhibit normal clearance and kinetics of infection
|
|
• mice infected with Citrobacter exhibit increased transient weight loss compared with wild-type mice and mice heterozygous for a knock-out allele
• however, mice exhibit normal clearance and kinetics of infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals die by the end of the first postnatal day (P0)
|
|
• in all embryos, brain size is larger than in controls, especially in the dorsal telencephalon
|
|
• based on cell fate analysis and molecular marker analysis, the intergeniculate leaflet (IGL) nucleus is expanded caudodorsally along the surface of the diencephalon at E16.5
|
|
• based on cell fate analysis and molecular marker analysis, the dorsal lateral geniculate (dLG) nucleus is expanded caudodorsally along the surface of the diencephalon at E16.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• partial; some pups survive postnatally
|
| N |
• brains are morphologically indistinguishable from controls
|
|
• expansion of the expression domain of the orphan receptor ROR alpha indicates that the the ventral posterior nucleus (VP) is increased in size
• in E18.5 brains, molecular marker analysis indicates that the entire postmitotic thalamus exhibits rostroventral identity
|
|
• based on thalamic labeling by cholera toxin B subunit injection, the volume of the dorsal lateral geniculate nucleus (dLG) is increased more than 3-fold compared to control neonatal animals; expansion of the expression domain of the orphan receptor ROR alpha indicates that the dLG is increased in size
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice show reduced density of alveoli
|
|
• alveoli are enlarged in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit emphysematous changes including enlarged alveoli with reduced alveolar density
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slightly less in LPS-stimulated marginal zone
• however, proliferation of alphaIgM-stimulated follicular B cells is not significantly different from that of wild-type cells
|
|
• FO I B cells
|
|
• total and FO II B cells
|
|
• slightly less in LPS-stimulated marginal zone
• however, proliferation of alphaIgM-stimulated follicular B cells is not significantly different from that of wild-type cells
|
|
• FO I B cells
|
|
• total and FO II B cells
|
|
• slightly less in LPS-stimulated marginal zone
• however, proliferation of alphaIgM-stimulated follicular B cells is not significantly different from that of wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit the same immune phenotype as in Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs Cd19tm1(cre)Cgn double heterozygotes
|
|
• mice exhibit the same immune phenotype as in Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs Cd19tm1(cre)Cgn double heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are larger and have thicker processes compared to astrocytes in injured wild-type mice
• however, lesion size is similar to that in injured wild-type mice
• at 35 days post injury astrocytes adjacent to the injury site remain hypertrophic unlike in wild-type controls
• increase in the number of axons present within the injury site
|
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are larger and have thicker processes compared to astrocytes in injured wild-type mice
• at 35 days post injury astrocytes adjacent to the injury site remain hypertrophic unlike in wild-type controls
|
|
• at 14 days post spinal injury formation of reactive astrocytes is increased compared to injured wild-type controls
|
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are larger and have thicker processes compared to astrocytes in injured wild-type mice
• at 35 days post injury astrocytes adjacent to the injury site remain hypertrophic unlike in wild-type controls
|
|
• at 14 days post spinal injury formation of reactive astrocytes is increased compared to injured wild-type controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are smaller and have thinner processes compared to astrocytes in injured wild-type mice
|
|
• lesion size is increased approximately 80% compared to wild-type mice following severe spinal cord injury
|
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are smaller and have thinner processes compared to astrocytes in injured wild-type mice
|
|
• at 14 days post spinal injury formation of reactive astrocytes is reduced compared to injured wild-type controls
|
|
• at 14 days post injury, astrocytes adjacent to spinal cord lesions are smaller and have thinner processes compared to astrocytes in injured wild-type mice
|
|
• at 14 days post spinal injury formation of reactive astrocytes is reduced compared to injured wild-type controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• parous mice develop mammary tumors 37 days after delivery of pups (at 140 days) unlike Tg(Wap-cre)1Gsc mice
• mammary tumors are heterogeneous (adenosquamous carcinoma, adenomyoepitheliomas, adenocarcinomas with squamouse metaplasia, adenocarcinomas, and adenocarcinomatosis)
|
|
|
• delayed due to reduced cell death
|
|
• parous mice develop mammary tumors 37 days after delivery of pups (at 140 days) unlike Tg(Wap-cre)1Gsc mice
• mammary tumors are heterogeneous (adenosquamous carcinoma, adenomyoepitheliomas, adenocarcinomas with squamouse metaplasia, adenocarcinomas, and adenocarcinomatosis)
|
|
|
• delayed due to reduced cell death
|
|
• parous mice develop mammary tumors 37 days after delivery of pups (at 140 days) unlike Tg(Wap-cre)1Gsc mice
• mammary tumors are heterogeneous (adenosquamous carcinoma, adenomyoepitheliomas, adenocarcinomas with squamouse metaplasia, adenocarcinomas, and adenocarcinomatosis)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 75% of mice die before 4 months of age
|
|
• in 25% of mice after 214 days unlike Tg(MMTV-cre)7Mul mice
• mammary tumors are heterogeneous (adenomyoepitheliomas)
|
|
• in 25% of mice after 214 days unlike Tg(MMTV-cre)7Mul mice
• mammary tumors are heterogeneous (adenomyoepitheliomas)
|
|
• in 25% of mice after 214 days unlike Tg(MMTV-cre)7Mul mice
• mammary tumors are heterogeneous (adenomyoepitheliomas)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected mice with this genotype are found
|
|
• the fraction of B and T cells expressing the recombined allele decreases during differentiation and maturation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slightly fewer than expected mice with this genotype are found
|
|
• the fraction of B and T cells expressing the recombined allele decreases during differentiation and maturation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no embryos are obtained at E12.5 or E14.5
|
|
• E9.5-E10.5 embryos are underdeveloped
|
|
• E9.5-E10.5 embryos are underdeveloped
|
|
• embryos exhibit a reduced content of mature CD71+Ter119+ primitive erythrocytes within the yolk sac vascular plexus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• viable with normal locomotor activity levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit loss of strength (hanging test) within 7-8 days following IP injection of TMX
|
|
• muscle from untreated mice has small irregular fibers
|
|
• heterogeneous fiber size distribution at time of euthanasia (9 days post TMX)
• muscle from untreated mice has small irregular fibers
|
|
• muscle from untreated mice has patches of centralized nuclei
|
|
• skeletal muscle tissues are mildly fibrotic at time of euthanasia (9 days post TMX)
|
|
• necrosis and phagocytosis are observed at time of euthanasia (9 days post TMX)
|
|
• Tamoxifen (TMX)-treated mice exhibit progressive myopathy
• untreated mice exhibit a mild muscle phenotype
|
|
• mice exhibit weight loss within 7-8 days following IP injection of TMX
|
|
• skeletal muscle tissues exhibit large infiltrates of mononuclear cells and loss of membrane integrity at time of euthanasia (9 days post TMX)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| facioscapulohumeral muscular dystrophy | DOID:11727 | J:256652 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice that survive past weaning die by 17 weeks of age from cancer
|
|
• only 8.3% (9 of 109) of pups at birth are double mutants and significant loss of these mice is seen at E16 but not at E10
|
|
• all double mutants develop cancer with a variety of tumor types
|
|
• non-T/non-B cell derived lymphoma is also seen
|
|
• most common type of tumor
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• pituitary hyperplasia was seen in 1 mouse
|
|
• most common type of tumor
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• at E16
|
|
• pituitary hyperplasia was seen in 1 mouse
|
|
• most common type of tumor
|
|
• most common type of tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice that survive past weaning die by 17 weeks of age from cancer
|
|
• only 5.6% (5 of 89) of pups at birth are double mutants and significant loss of these mice is seen at E16 but not at E10
|
|
• all double mutants develop cancer with a variety of tumor types
|
|
• non-T/non-B cell derived lymphoma is also seen
|
|
• most common type of tumor
|
|
• some mice develop medulloblastomas
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• at E16
|
|
• most common type of tumor
|
|
• some mice develop medulloblastomas
|
|
• most common type of tumor
|
|
• most common type of tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice that survive past weaning die by 17 weeks of age from cancer
|
|
• only 12.5% (17 of 136) of pups at birth are double mutants and significant loss of these mice is seen at E16 but not at E10
|
|
• all double mutants develop cancer with a variety of tumor types
|
|
• non-T/non-B cell derived lymphoma is also seen
|
|
• most common type of tumor
|
|
• some mice develop medulloblastomas
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• hyperplasia of the duodenum was seen in 2 mice
|
|
• at E10 and E16, many embryos appear smaller than control littermates
|
|
• at E16
|
|
• most common type of tumor
|
|
• some mice develop medulloblastomas
|
|
• most common type of tumor
|
|
• most common type of tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are runted
|
|
• mice treated with an alpha IL-1R blocking antibody show weight gain
|
|
• increase in neutrophils in the spleen and lymph nodes
|
|
• increase in monocytes in the spleen and lymph nodes
|
|
• mice exhibit increased cytokine levels, with IL-18 having the greatest increase
|
|
• mice develop joint swelling
• mice treated with an alpha IL-1R blocking antibody show deceased joint swelling
|
|
• increase in neutrophils in the spleen and lymph nodes
|
|
• increase in monocytes in the spleen and lymph nodes
|
|
• mice exhibit increased cytokine levels, with IL-18 having the greatest increase
|
|
• mice develop joint swelling
• mice treated with an alpha IL-1R blocking antibody show deceased joint swelling
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are runted
|
|
• mice exhibit elevation of neutrophils in tissues
|
|
• mice exhibit elevation of monocytes in tissues
|
|
• mice exhibit elevation of neutrophils in tissues
|
|
• mice exhibit elevation of monocytes in tissues
|
| N |
• mice do not develop joint swellings
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Cervical vertebrae fusions in Gt(ROSA)26Sortm1Fan/Gt(ROSA)26Sor+ Tg(T-cre)1Lwd/0 mice
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Gt(ROSA)26Sortm1(sb11)Njen mice
|
|
• in one mouse
|
|
• liver tumors metastasize to the lungs
|
|
• 23 tumors in 62 with mice greater prevalent in male than female mice
|
|
• 58 tumors in 62 mice with greater prevalent in male than female mice
|
|
• 23 adenomas with multiple locations develop in 62 mice
|
|
• 7 hemangiomas with multiple locations develop in 62 mice
|
|
• in 11% of mice (7 tumors in 62 mice)
|
|
• 3 tumors in 62 mice
|
|
• 5 tumors in 62 mice
|
|
• in one mouse
|
|
• mice develop carcinomas in the colon (1 tumors in 62 mice), lung (3 in 62), mammary gland (5 in 62), salivary gland (1 in 62), preputial gland (12 in 62), parathyroid (1 in 62), and nasal cavity (1 in 62)
|
|
• in one mouse
|
|
• 3 tumors in 62 mice
|
|
• one mouse developed a squamous cell carcinoma in the clitoral gland
• one mouse developed a squamous cell carcinoma in the salivary gland
|
|
• 27 tumors in 62 mice
|
|
• one mouse developed a melanoma
|
|
• 2 sarcomas with multiple locations develop in 62 mice
|
|
• 4 tumors in 62 mice
|
|
• in one mouse
|
|
• 27 tumors in 62 mice
|
|
• in one mouse
|
|
• 3 tumors in 62 mice
|
|
• liver tumors metastasize to the lungs
|
|
• 23 tumors in 62 with mice greater prevalent in male than female mice
|
|
• 58 tumors in 62 mice with greater prevalent in male than female mice
|
|
• 3 tumors in 62 mice
|
|
• 3 tumors in 62 mice
|
|
• 3 tumors in 62 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when tamoxifen is administered after 3 weeks of age myopathy develops by 12 months
|
|
• when tamoxifen is administered after 3 weeks of age tumors develop in the extremities of 100% of mice by 8 weeks of age
• tumors arise from the periosteal/perichondrial layer as well as within musculature
• clear cell morphology or spindle cell morphology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the mean overall thickness of the skin of E18.5 embryos is reduced by 10% compared to wild-type embryos
|
|
• the mean thickness of the epidermis of E18.5 embryos is slightly but significantly reduced by 4% compared to wild-type embyros
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following 2 and 5 weeks of tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit reduced numbers of podocytes compared with wild-type mice
|
|
• tamoxifen-treated mice exhibit reduced numbers of podocytes compared with wild-type mice
|
|
• in some mice 5 weeks after induction with tamoxifen
|
|
• following 2 and 5 weeks of tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop acinar to ductal metaplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• responses to acute noxious heat, cold, mechanical and chemical stimulation after diphtheria toxin (DTX) treatment are similar to control littermates
• normal motor function is observed following DTX treatment
• injection of capsaicin to the cheek induces normal pain-invoked facial wiping behavior in DTX-treated animals comparable to controls
• cheek injection of beta-alanine induces robust scratching response in DTX-treated mice similar to the behavior in treated controls
|
|
• scratching behavior is reduced relative to controls in DTX-treated mice after injection of alpha-methyl-serotonin or endothelin-1
• in models of dry skin pruritus and allergic chronic itch, DTX-treated mice show reduced scratching behavior compared to controls
• injection of chloroquine into cheeks of DTX-treated mice abolishes the hindpaw cheek-scratching elicited in DTX-treated controls
• hindpaw scratching induced by histamine administration to the cheek is reduced in DTX-treated mice relative to treated controls
• subcutaneous injection of histamine into the napes of DTX-treated mice results in a reduced scratching behavior compared to DTX-treated controls
• site-directed scratching is abolished in DTX-treated mutants following injection of either BAN8-22 or SLIGRL-NH2 (pruritogens that activate Mrgprx1)
• after subcutaneous cloroquine injection into the necks of DTX-treated mice, site-directed scratching is significantly reduced compared to DTX- and cholorquine-treated control littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tibia show a decrease in osteoclast-covered bone surface
• however, osteoclast number and osteoblast-covered surface and number are unaltered
|
|
|
• trabecular bone volume is increased in lumbar spine of females
|
|
• males exhibit decreased cortical porosity in femurs while females exhibit increased cortical porosity in femurs
• however, trabecular bone is unaffected
|
|
|
• trabecula number is increased in lumbar spine of females
|
|
|
• trabecular separation in lumbar spine of females is decreased
|
|
|
• trabecular thickness is increased in lumbar spine of females
|
|
|
• tibial endocortical bone surface shows an increase in endosteal mineralizing surface
|
|
|
• trabecular bone surface of vertebral bodies shows a decrease in mineralizing surface and bone formation rate
• however, biomechanical properties of femurs are similar to controls
|
|
|
• tibia show a decrease in osteoclast-covered bone surface
• however, osteoclast number and osteoblast-covered surface and number are unaltered
|
|
N |
• mice exhibit normal calvarial bone thickness and porosity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal behavior
|
| N |
• mice exhibit normal body weight
|
| N |
• mice produce normal levels of proinflammatory cytokines when provoked with inflammasome-activating stimuli
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
|
|
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Early greying in Pikfyvetm2.1Tssk/Pikfyvetm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0 Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor+ mice
|
• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50
• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected
|
|
• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50
• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal collagen structure in Vipas39tm1c(KOMP)Mbp/Vipas39tm1c(KOMP)Mbp Gt(ROSA)26Sortm1(cre/ERT2)Tyj/Gt(ROSA)26Sor+, and Vps33btm1.1Arte/Vps33btm1.1Arte Gt(ROSA)26Sortm1(cre/ERT2)Tyj/Gt(ROSA)26Sor+ mouse tail tendon
|
• in tamoxifen-treated mice
|
|
• in the spleen of tamoxifen-treated mice
|
|
• most bone marrow megakaryocytes in tamoxifen-treated mice lack immature granules and alpha granules
• some small alpha-granule-like structures are present in megakaryocytes of tamoxifen-treated mice
• megakaryocytes in tamoxifen-treated mice contain a large number of lamellar structures located close to the nucleus or to the periphery of the cells
• however, some megakaryocytes contain normal numbers of alpha granules
|
|
• in the splenic red pulp and bone marrow of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• lacking in most platelets of tamoxifen-treated mice
• however, a subpopulation of platelets have normal alpha-granules
|
|
• without a change in platelet half-life in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the spleen of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the spleen of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
| N |
• no visceral abnormalities are observed after tamoxifen treatment
|
|
• in tamoxifen-treated mice
|
|
• 5 weeks after tamoxifen treatment
(J:222766)
• mice develop dry skin 4 weeks after tamoxifen treatment
(J:236095)
|
|
• mild to severe 5 weeks after tamoxifen treatment
(J:222766)
• mice develop scaly skin 4 weeks after tamoxifen treatment
(J:236095)
|
|
• occasional macerated skin lesions 5 weeks after tamoxifen treatment
|
|
• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed
• AFM showed a greater level of distortion with a far more irregular profile and height variation than in mice homozygous for Vipas39tm1c(KOMP)Mbp and heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure
|
|
• in tamoxifen-treated mice
|
|
• in 9 of 15 tamoxifen-treated mice
• however, there is no sign of spontaneous bleeding
|
|
• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed
• AFM showed a greater level of distortion with a far more irregular profile and height variation than in mice homozygous for Vipas39tm1c(KOMP)Mbp and heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the spleen of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in the spleen of tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ARC syndrome | DOID:0050763 |
OMIM:PS208085 |
J:222766 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E18.5, cortices show an apical shift in the expression domain of Cux2, a marker of intermediate progenitors that give rise to upper layer (UL) 2/3 cortical projection neurons (CPNs)
• however, TdTomato levels are largely normal at E14.5, E16.5 and E18.5
|
|
• in culture, primary upper layer CPNs show a progressive reduction in neurite outgrowth and branching complexity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal collagen structure in Vipas39tm1c(KOMP)Mbp/Vipas39tm1c(KOMP)Mbp Gt(ROSA)26Sortm1(cre/ERT2)Tyj/Gt(ROSA)26Sor+, and Vps33btm1.1Arte/Vps33btm1.1Arte Gt(ROSA)26Sortm1(cre/ERT2)Tyj/Gt(ROSA)26Sor+ mouse tail tendon
|
• mice develop scaly skin 4 weeks after tamoxifen treatment
|
|
• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed
• AFM showed a large increase in height with swelling causing large jumps in profile analysis
• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure
|
|
• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed
• AFM showed a large increase in height with swelling causing large jumps in profile analysis
• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure
|
| N |
• no visceral abnormalities are observed after tamoxifen treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ARC syndrome | DOID:0050763 |
OMIM:PS208085 |
J:236095 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 41 days post pIpC treatment
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the thymus at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months in pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• nearly all B cells are arrested in the early pro-B stage of pIpC-treated mice
|
|
• in the thymus of pIpC-treated mice
|
|
• in the spleen of pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• at 6 months in pIpC-treated mice
|
|
• in the thymus of pIpC-treated mice
|
|
• immature single positive cells in the thymus of pIpC-treated mice
|
|
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months in pIpC-treated mice
|
|
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the spleen, interstitial and perivascular space of the kidney, perivascular cuffs in the liver, meninges surrounding the brain, thymus, stomach and intestine at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the intestine at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the stomach at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the meninges surrounding the brain at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the intestine at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the stomach at 6 months in pIpC-treated mice
|
|
• pIpC-treated mice rapidly develop and succumb to acute leukemia
|
|
• in diseased pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months in pIpC-treated mice
|
|
• lymphoid infiltration in the meninges surrounding the brain at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the thymus at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• severely at 6 months in pIpC-treated mice
|
|
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months in pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• nearly all B cells are arrested in the early pro-B stage of pIpC-treated mice
|
|
• in the thymus of pIpC-treated mice
|
|
• in the spleen of pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
• at 6 months in pIpC-treated mice
|
|
• in the thymus of pIpC-treated mice
|
|
• immature single positive cells in the thymus of pIpC-treated mice
|
|
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months in pIpC-treated mice
|
|
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months in pIpC-treated mice
|
|
• in diseased pIpC-treated mice
|
|
• lymphoid infiltration in the thymus at 6 months in pIpC-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal T cell differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• E14.5 embryos show slow development in the cortex, where apical radial glial cells (RGCs; SOX2+) tend to accumulate at the expense of committed intermediate neural progenitors (INPs; TBR2+) and early differentiating neurons (DCX+)
|
|
• cortical radial glial cells exhibit a simpler neuronal shape
|
|
• apical radial glial cells (RGCs; SOX2+) tend to accumulate in the cortex in E14.5 embryos
|
|
• P30 mice exhibit reduced brain structure (e.g. cortical wall)
|
|
• P30 mice exhibit increased ventricle volume
|
|
• P30 mice exhibit microcephaly
|
|
• E14.5 embryos show slow development in the cortex, where apical radial glial cells (RGCs; SOX2+) tend to accumulate at the expense of committed intermediate neural progenitors (INPs; TBR2+) and early differentiating neurons (DCX+)
|
|
• cortical radial glial cells exhibit a simpler neuronal shape
|
|
• apical radial glial cells (RGCs; SOX2+) tend to accumulate in the cortex in E14.5 embryos
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Schinzel Giedion syndrome | DOID:0070509 |
OMIM:269150 |
J:363042 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 8-fold in severe cases after doxycycline withdrawal
|
|
• mice not fed doxycycline exhibit die before 3 months of age unlike wild-type mice
• however, mice fed doxycycline are alive at 3 months of age
|
|
• after doxycycline withdrawal, thymus structure is altered by invasion of neoplastic cells unlike in similarly treated wild-type mice
|
|
• after doxycycline withdrawal
|
|
• 20-fold in severe cases after doxycycline withdrawal
|
|
• in 4 of 7 mice at 3 months
|
|
• after doxycycline withdrawal, spleen abnormalities are due to malignant invasion of red pulp unlike in similarly treated wild-type mice
|
|
• 8-fold in severe cases after doxycycline withdrawal
|
|
• after doxycycline withdrawal
|
|
• two months after doxycycline withdrawal and in mice not fed doxycycline
|
|
• mice fed doxycycline after a period of not consuming it exhibit regression of lymphomas associated with increased apoptosis of tumor cells and decreased cell proliferation compared with untreated mice
|
|
• after doxycycline withdrawal, mice exhibit malignant invasion in the spleen, thymus, peripheral blood, and other organs, especially the liver and less frequently the kidney, unlike in similarly treated wild-type mice
• however, mice fed doxycycline exhibit remission of tumors and tumor-associated pathologies
|
|
• mice not fed doxycycline exhibit external signs of lymphoma (lymphadenopathy and/or paresis of rear limbs) unlike wild-type mice
• however, mice fed doxycycline do not exhibit pathologies associated with lymphomas
|
|
• two months after doxycycline withdrawal
|
|
• paresis in the hindlimbs two months after doxycycline withdrawal
|
|
• after doxycycline withdrawal, mice exhibit extended bone marrow in the thoracic and lumbar vertebrae, femur, sternum, and hard palate causing paresis, bone fractures, and invasion of surrounding tissue unlike similarly treated wild-type mice
|
|
• two months after doxycycline withdrawal
|
|
• after doxycycline withdrawal, thymus structure is altered by invasion of neoplastic cells unlike in similarly treated wild-type mice
|
|
• after doxycycline withdrawal
|
|
• 20-fold in severe cases after doxycycline withdrawal
|
|
• at 3 months
|
|
• at 3 months
|
|
• in 4 of 7 mice at 3 months
|
|
• after doxycycline withdrawal, spleen abnormalities are due to malignant invasion of red pulp unlike in similarly treated wild-type mice
|
|
• 8-fold in severe cases after doxycycline withdrawal
|
|
• after doxycycline withdrawal
|
|
• two months after doxycycline withdrawal
|
|
• after doxycycline withdrawal, thymus structure is altered by invasion of neoplastic cells unlike in similarly treated wild-type mice
|
|
• after doxycycline withdrawal
|
|
• 20-fold in severe cases after doxycycline withdrawal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die around E11.5
|
|
• dilated at E10.5 to E11.5
• fragile blood vesels
|
|
• bleeding in some mice at E10.5 to E11.5
|
|
• abnormal hematopoiesis that biases the developmental program towards endothelial cells
|
|
• dilated at E10.5 to E11.5
• fragile blood vesels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• constitutively active Map2k1(MEK) rescues thymocyte development restoring single positive thymocyte and splenic T cell populations
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• proliferation in the GCM2-negative thymus-fated domain of the 3rd pharyngeal pouch is reduced at E11.5
|
|
• marker analysis at E15.5 indicates an early block in thymic epithelial cell differentiation, with impaired differentiation of both cortical thymic epithelial cell and medullary thymic epithelial cell lineages and an accumulation of early thymic epithelial cell progenitors
• thymocytes show a partial block at the DN3 to DN4 transition at E15.5 indicating a partial differentiation arrest at the DN3 stage
|
|
• accumulation of early thymic epithelial cell progenitors
|
|
• fetal thymi are severely hypoplastic throughout development and remain so in the postnatal period
|
|
• total thymocyte cellularity is decreased by about 5-fold in E15.5 thymi
|
|
• marker analysis at E15.5 indicates an early block in thymic epithelial cell differentiation, with impaired differentiation of both cortical thymic epithelial cell and medullary thymic epithelial cell lineages and an accumulation of early thymic epithelial cell progenitors
• thymocytes show a partial block at the DN3 to DN4 transition at E15.5 indicating a partial differentiation arrest at the DN3 stage
|
|
• accumulation of early thymic epithelial cell progenitors
|
|
• fetal thymi are severely hypoplastic throughout development and remain so in the postnatal period
|
|
• total thymocyte cellularity is decreased by about 5-fold in E15.5 thymi
|
|
• marker analysis at E15.5 indicates an early block in thymic epithelial cell differentiation, with impaired differentiation of both cortical thymic epithelial cell and medullary thymic epithelial cell lineages and an accumulation of early thymic epithelial cell progenitors
• thymocytes show a partial block at the DN3 to DN4 transition at E15.5 indicating a partial differentiation arrest at the DN3 stage
|
|
• accumulation of early thymic epithelial cell progenitors
|
|
• fetal thymi are severely hypoplastic throughout development and remain so in the postnatal period
|
|
• total thymocyte cellularity is decreased by about 5-fold in E15.5 thymi
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduction in the number of mature resting plasma cells in the bone marrow following immunization with TNP-KLH and treatment with tamoxifen
|
|
• the number of P3-plasma cells in the blood in elevated in TNP-KLH immunized and boosted mice treated with tamoxifen
|
|
• the number of P1-plasmablasts is diminished in the spleen in TNP-KLH immunized and boosted mice treated with tamoxifen
|
|
• reduction in EdU+ mature P3-plasma cells in the bone marrow of TNP-KLH immunized and tamoxifen treated mice indicating reduced mature plasma turnover
• however, the EdU+ P2-plasma cell subset is unchanged
|
|
• reduction in the number of mature resting plasma cells in the bone marrow following immunization with TNP-KLH and treatment with tamoxifen
|
|
• the number of P3-plasma cells in the blood in elevated in TNP-KLH immunized and boosted mice treated with tamoxifen
|
|
• the number of P1-plasmablasts is diminished in the spleen in TNP-KLH immunized and boosted mice treated with tamoxifen
|
|
• reduction in EdU+ mature P3-plasma cells in the bone marrow of TNP-KLH immunized and tamoxifen treated mice indicating reduced mature plasma turnover
• however, the EdU+ P2-plasma cell subset is unchanged
|
|
• mice immunized and boosted with TNP-KLH and treated with tamoxifen exhibit a reduction in the CD138/Taci+ plasmablast/plasma cell population, notably the CD19-negative mature resting P3-plasma cells in the spleen and bone marrow
• mice immunized and boosted with TNP-KLH and treated with tamoxifen show a decrease in total number of antibody secreting cells in the bone marrow
• however, the numbers of NTP-specific antibody secreting in the spleen and bone marrow remain unchanged after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• leukemia-initiating cells plated in methylcellulose cultures in the presence of tamoxifen exhibit decreased blast colony number and loss of blast colony formation due to increased apoptosis compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• following tamoxifen treatment at E10.5 expression analysis indicates a delay in germ cell differentiation at E14.5 that is no longer detectable by E16.5
|
|
|
• following tamoxifen treatment at E10.5 expression analysis indicates a delay in germ cell differentiation at E14.5 that is no longer detectable by E16.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 1 week, tamoxifen-treated mice exhibit decreased regulatory T cell number compared with control mice that is thymus independent and associated with reduced cell proliferation
|
|
• regulatory T cells from tamoxifen-treated mice exhibit reduced suppression function and a 2-fold reduction in proliferation compared with wild-type cells
|
|
• after 1 week, tamoxifen-treated mice exhibit decreased regulatory T cell number compared with control mice that is thymus independent and associated with reduced cell proliferation
|
|
• regulatory T cells from tamoxifen-treated mice exhibit reduced suppression function and a 2-fold reduction in proliferation compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Testicular degeneration in Nabp2tm1.1Kkha/Nabp2tm1.1Kkha Gt(ROSA)26Sortm9(cre/ESR1)Arte/Gt(ROSA)26Sor+ mice
|
• in tamoxifen-treated mice
|
|
N |
• tamoxifen-treated female mice exhibit normal fertility
|
|
|
• premature sloughing from the supporting Sertoli cells in tamoxifen-treated mice
|
|
|
• due to apoptosis and premature sloughing from the supporting Sertoli cells in tamoxifen-treated mice
• decreased elongated spermatids
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• bilateral degeneration; tubules showed degenerate, sometimes vacuolated, or
necrotic spermatogenic cells, the latter with pyknotic nuclei and
hypereosinophilic cytoplasm, or apoptotic body formation in tamoxifen-treated mice
|
|
|
• from tamoxifen-treated mice with longer intervals between litters
|
|
|
• in tamoxifen-treated mice
|
|
• splenic and metastatic B lymphomas, T cell lymphoma in thymus, hepatocellular carcinoma and B or T lymphoblastic leukemia in 11 of 35 of tamoxifen-treated mice
|
|
• in thymus of some tamoxifen-treated mice
|
|
• in some tamoxifen-treated mice
|
|
• B or T lymphoblastic leukemia in some tamoxifen-treated mice
|
|
• splenic and metastatic B lymphomas in some tamoxifen-treated mice
|
|
|
• premature sloughing from the supporting Sertoli cells in tamoxifen-treated mice
|
|
|
• due to apoptosis and premature sloughing from the supporting Sertoli cells in tamoxifen-treated mice
• decreased elongated spermatids
|
|
• tamoxifen-treated mice exposed to ionizing radiation exhibit distended crypt lumina lined by attenuated enterocytes, desquamated necrotic cellular debris and a small increase of cells near deep crypts with apoptotic bodies
• however, blood counts are normal in irradiated tamoxifen-treated mice
|
|
• in irradiated tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• at E14.5 and E18.5
|
|
• tamoxifen-treated mice exposed to ionizing radiation exhibit distended crypt lumina lined by attenuated enterocytes, desquamated necrotic cellular debris and a small increase of cells near deep crypts with apoptotic bodies
|
|
• in irradiated tamoxifen-treated mice
|
|
• in thymus of some tamoxifen-treated mice
|
|
• in irradiated tamoxifen-treated mice
|
|
• in thymus of some tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• in tamoxifen-treated mice
|
|
|
• bilateral degeneration; tubules showed degenerate, sometimes vacuolated, or
necrotic spermatogenic cells, the latter with pyknotic nuclei and
hypereosinophilic cytoplasm, or apoptotic body formation in tamoxifen-treated mice
|
| N |
• blood counts are normal in irradiated tamoxifen-treated mice
|
|
• in irradiated tamoxifen-treated mice
|
|
• in thymus of some tamoxifen-treated mice
|
|
• tamoxifen-treated mice exposed to ionizing radiation exhibit distended crypt lumina lined by attenuated enterocytes, desquamated necrotic cellular debris and a small increase of cells near deep crypts with apoptotic bodies
• however, blood counts are normal in irradiated tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in some tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• tamoxifen-treated mice exhibit functionally active NK T cells
|
|
|
• following exposure to NP-KLH with alpha-GalCer, germinal center B cells from tamoxifen-treated mice fail to exhibit an increase in numbers unlike in wild-type mice
|
|
|
• tamoxifen-treated mice exhibit reduced late primary antibody response on transfer of OT-II CD4+ T cells compared with wild-type
|
|
|
• following immunization with NP-KLH and alpha-GalCer, tamoxifen-treated mice exhibit reduced NP-specific IgG that is more severe than in Sh2d1atm1Cpt homozygotes
|
|
|
• following exposure to NP-KLH with alpha-GalCer, tamoxifen treated mice produce less anti-NP-IgM compared with wild-type mice
|
|
|
• following exposure to NP-KLH with alpha-GalCer, germinal center B cells from tamoxifen-treated mice fail to exhibit an increase in numbers unlike in wild-type mice
|
|
|
• following immunization with NP-KLH and alpha-GalCer, tamoxifen-treated mice exhibit reduced NP-specific IgG that is more severe than in Sh2d1atm1Cpt homozygotes
|
|
|
• following exposure to NP-KLH with alpha-GalCer, tamoxifen treated mice produce less anti-NP-IgM compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• tamoxifen-treated mice exhibit functionally active NK T cells
|
|
|
• following exposure to NP-KLH with alpha-GalCer, germinal center B cells from tamoxifen-treated mice fail to exhibit an increase in numbers unlike in wild-type mice
|
|
|
• tamoxifen-treated mice exhibit reduced late primary antibody response on transfer of OT-II CD4+ T cells compared with wild-type
|
|
|
• following immunization with NP-KLH and alpha-GalCer, tamoxifen-treated mice exhibit reduced NP-specific IgG that is more severe than in Sh2d1atm1Cpt homozygotes
|
|
|
• following exposure to NP-KLH with alpha-GalCer, tamoxifen treated mice produce less anti-NP-IgM compared with wild-type mice
|
|
|
• following exposure to NP-KLH with alpha-GalCer, germinal center B cells from tamoxifen-treated mice fail to exhibit an increase in numbers unlike in wild-type mice
|
|
|
• following immunization with NP-KLH and alpha-GalCer, tamoxifen-treated mice exhibit reduced NP-specific IgG that is more severe than in Sh2d1atm1Cpt homozygotes
|
|
|
• following exposure to NP-KLH with alpha-GalCer, tamoxifen treated mice produce less anti-NP-IgM compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treatment induces mild but progressive hematological defects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• prominent basophilic stippling after tamoxifen treatment
|
|
• changes in leukocyte numbers are consistent with a chronic myelomonocytic leukemia (CMML)-like disease
• transplantation of bone marrow cells into lethally irradiated congenic wild-type mice followed by tamoxifen treatment also results in a CMML-like disease
|
|
• seen in all mice 4 weeks after the last tamoxifen injection
|
|
• at 4 weeks after the last tamoxifen injection peripheral blood shows cytological features consistent with myelodysplasia
• increase in the number of lineage-negative ScaI? c-Kit+ myeloid progenitor cells in the spleen and bone marrow as early as 2 weeks after the last tamoxifen treatment
• atypical immature cells with myelomonocytic features detected after tamoxifen treatment
|
|
• expansion of the myeloid lineage in the spleen, lymph nodes and bone marrow at 4 weeks after the last tamoxifen injection
|
|
• 4 weeks after the last tamoxifen injection
|
|
• signs of erythroid dysplasia after tamoxifen treatment
|
|
• prominent basophilic stippling after tamoxifen treatment
|
|
• at 4 weeks after the last tamoxifen injection peripheral blood shows cytological features consistent with ineffective erythropoiesis
|
|
• after tamoxifen treatment
|
|
• after tamoxifen treatment
|
|
• bilobed granulocytes after tamoxifen treatment
|
|
• hypersegmented and hyposegmented neutrophils after tamoxifen treatment
|
|
• 4 weeks after the last tamoxifen injection
|
|
• detected as early as 1 week after the last tamoxifen treatment
|
|
• giant platelets detected after tamoxifen treatment
|
|
• elevated total leukocyte numbers at 4 weeks after the last tamoxifen injection
|
|
• 4 weeks after the last tamoxifen injection
|
|
• in the spleen and bone marrow as early as 2 weeks after the last tamoxifen treatment
|
|
• cells taken from tamoxifen treated mice fail to reconstitute the bone marrow of lethally irradiated congenic wild-type mice
|
|
• cultured cells collected 1 month after the last tamoxifen treatment produce fewer colonies and replated cells do not produce well formed colonies
|
|
• neutrophilic inflammation and infiltration of myeloblastic cells after tamoxifen treatment
|
|
• seen in all mice 4 weeks after the last tamoxifen injection
|
|
• at 4 weeks after the last tamoxifen injection peripheral blood shows cytological features consistent with myelodysplasia
• increase in the number of lineage-negative ScaI? c-Kit+ myeloid progenitor cells in the spleen and bone marrow as early as 2 weeks after the last tamoxifen treatment
• atypical immature cells with myelomonocytic features detected after tamoxifen treatment
|
|
• expansion of the myeloid lineage in the spleen, lymph nodes and bone marrow at 4 weeks after the last tamoxifen injection
|
|
• bilobed granulocytes after tamoxifen treatment
|
|
• hypersegmented and hyposegmented neutrophils after tamoxifen treatment
|
|
• 4 weeks after the last tamoxifen injection
|
|
• elevated total leukocyte numbers at 4 weeks after the last tamoxifen injection
|
|
• 4 weeks after the last tamoxifen injection
|
|
• microthrombi in the heart after tamoxifen treatment
|
|
• multifocal necrosis after tamoxifen treatment
|
|
• multifocal necrosis after tamoxifen treatment
|
|
• neutrophilic inflammation and infiltration of myeloblastic cells after tamoxifen treatment
|
|
• seen in all mice 4 weeks after the last tamoxifen injection
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| myelodysplastic syndrome | DOID:0050908 |
OMIM:614286 |
J:187380 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• 48 and 72 hours after tamoxifen treatment
|
|
• slight in tamoxifen treated mice at 48 hours of both erythroid and myeloid cells
• further decrease after 72 hours in tamoxifen-treated mice
|
|
• 72 hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment
|
|
• 48 and 72, but not 24, hours after tamoxifen treatment
|
|
• 48 and 72, but not 24, hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• 72 hours after tamoxifen treatment
|
|
• decreased at 72 hours in tamoxifen-treated mice
|
|
• 72 hours after tamoxifen treatment, mice exhibit atrophy of the small and large intestine mucosa with sloughing of mucosal epithelial cells and/or necrotic decries in the crypts compared with control mice
|
|
• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice
|
|
• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice
|
|
• 48 hours after tamoxifen treatment, mice exhibit increased single cell necroses at the base of villi in the small intestine compared with control mice
|
|
• 72 hours after tamoxifen treatment, mice exhibit atrophy of the stomach mucosa predominantly in the pyloric region and characterized by exfoliation of necrotic epithelial cells into the gastric lumen and thinning of the gastric epithelial cells, especially the gastric gland epithelium, compared with control mice
|
|
• increased total protein in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• total and albumin to globulin ratio in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice
• 48 hours after tamoxifen treatment, mice exhibit increased single cell necroses at the base of villi in the small intestine compared with control mice
• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with wild-type mice
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus and spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• slight at 72 hours in tamoxifen-treated mice
|
|
• decreased at 72 hours in tamoxifen-treated mice
|
|
• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice
|
|
• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice
|
|
• increased adrenal gland weight at 72 hours after tamoxifen treatment
|
|
• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• 48 and 72 hours after tamoxifen treatment
|
|
• slight at 72 hours in tamoxifen-treated mice
|
|
• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• 48 and 72 hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment
|
|
• 48 and 72, but not 24, hours after tamoxifen treatment
|
|
• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice
|
|
• 72 hours after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased under Th1-, Th17- and induced regulatory T cell-skewing conditions following tamoxifen-treatment
|
|
• reduced under Th17-skewing conditions following tamoxifen-treatment
|
|
• reduced regulatory T cell differentiation under induced regulatory T cell-skewing conditions following tamoxifen-treatment
|
|
• increased under Th1-, Th17- and induced regulatory T cell-skewing conditions following tamoxifen-treatment
|
|
• reduced under Th17-skewing conditions following tamoxifen-treatment
|
|
• reduced regulatory T cell differentiation under induced regulatory T cell-skewing conditions following tamoxifen-treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• beyond the pachytene stage in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• one third normal in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• beyond the pachytene stage in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• one third normal in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• expansion of immature megakaryocytes and blocked differentiation in pIpC-treated mice
|
|
• mild in pIpC-treated mice
|
|
• in the bone marrow and spleen of pIpC-treated mice
|
|
• 2-fold in the bone marrow in pIpC-treated mice
|
|
• larger in size in pIpC-treated mice compared to in control mice
|
|
• in pIpC-treated mice
|
|
• expansion of immature megakaryocytes and blocked differentiation in pIpC-treated mice
|
|
• mild in pIpC-treated mice
|
|
• in the bone marrow and spleen of pIpC-treated mice
|
|
• mild in pIpC-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal brain weight
• mice do not develop seizures
|
|
• astrocytes exhibit increased mTor signaling-dependent proliferation compared to in control cells
|
| N |
• mice exhibit normal body weight
|
|
• astrocytes exhibit increased mTor signaling-dependent proliferation compared to in control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
• however, induced hypoglycemia is transient
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• increased beta cell apoptosis and reduced proliferation in tamoxifen-treated mice
• beta cells from tamoxifen-treated mice exhibit glucotoxicity including increased expression of ER and oxidative stress markers compared to in control cells
• however, GFP- beta cells exhibit increased proliferation and mice treated with a selective inhibitor of calcineurin (tacrolimus; FK-506) or a GLP-1 receptor agonist (liraglutide) exhibit reduced beta cell apoptosis and dysfunction
|
|
• reduced proliferation in tamoxifen-treated mice
• however, GFP- beta cells exhibit increased proliferation
|
|
• reduced proliferation in tamoxifen-treated mice
• however, GFP- beta cells exhibit increased proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop a diseased phenotype beginning 4-6 weeks following tamoxifen treatment, with multiple organ failure leading to lethality
|
|
• mice develop respiratory distress 4-6 weeks after tamoxifen treatment
|
|
• mice exhibit loss of mobility 4-6 weeks after tamoxifen treatment
|
|
• tamoxifen-treated mice exhibit mitochondrial aggregation in renal cortex and liver parenchyma and small mitochondria aggregation in Schwann cell cytoplasm of the sciatic nerve, most likely indicating un-fused mitochondria
|
|
• mice develop bloating due to ascites accumulation 4-6 weeks after tamoxifen treatment
|
|
• mice exhibit skin follicle erection 4-6 weeks after tamoxifen treatment
|
|
• tamoxifen-treated mice show abnormal myelination of the tibial nerve, with abnormal myelin configurations surrounding some axons
• tibial nerves of tamoxifen-treated mice show double myelinated axons in which the inner portion of the outer sheath is decompacting
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percent GFP+ cells in irradiated tamoxifen-treated mice reconstituted with irradiated lymphocyte and HSPC compartments is greater than in mice reconstituted with only the lymphocyte compartment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are phenotypically indistinguishable from control littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA
|
|
• following irradiation, the proportion of GFP+ cells in the hematopoietic stem and progenitor cell compartment and myeloid and lymphoid lineages of tamoxifen-treated mice is increased compared to un-irradiated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged
|
|
• excessive limb growth
|
|
• enlarged
|
|
• ectopic skeletal elements in the fore- and hindlimbs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal appendage development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• body weight of neonates is normal
• growth retardation after birth
• body weight is 50% of controls by three months
• pancreas weight/body weight ratio is normal
|
|
• by 6 weeks of age loss of response to injected glucose
|
|
• dramatic lowering of glucose levels after insulin injection
|
|
• blood glucose is over 200mg/dl within 2 weeks of birth
• progressively increases to over 600mg/dl by 2 months
|
|
• levels become undetectable as diabetes becomes more severe
|
|
• significantly elevated early in diabetes development
|
|
• plasma insulin levels decrease with time
|
|
• alpha cells infiltrate center of islets after the onset of diabetes
|
|
• are lost as diabetes becomes more severe
|
|
• beta cells are lost as diabetes develops
|
|
• number of islet is reduced by 50% early in diabetes and by more than 90% later
|
|
• islet mass decreases to about 10% of controls
|
|
• pancreas weight relative to controls becomes reduced over time
• pancreas weight/body weight ratio is normal
|
|
• insulin content of pancreas drops to about 10% of control levels
|
|
• by 6 weeks of age loss of response to injected glucose
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| permanent neonatal diabetes mellitus | DOID:0060639 |
OMIM:606176 |
J:146650 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die during the first week of life
|
|
• at birth
|
|
• mild at birth
|
|
• reduced beta cell area at E16.5 and birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• similar to mice homozygous for Irx3tm1Hui
|
|
• similar to mice homozygous for Irx3tm1Hui
|
|
• similar to mice homozygous for Irx3tm1Hui
|
|
• expression analysis indicates browning of white adipose
|
|
• similar to mice homozygous for Irx3tm1Hui
|
|
• similar to mice homozygous for Irx3tm1Hui
|
| N |
• food intake and locomotor activity are similar to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a minor but significant increase in the number of granulocytes in the blood
|
|
• despite high levels of IL-17A expression by T cells, there is no difference in onset or severity of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide (MOG) compared to controls
|
|
• increased numbers of neutrophils are recruited into the spleen compared to controls after immunization with MOG peptide
|
|
• immunization with MOG peptide plus adjuvant leads a highly significant increase in serum IL-17A levels
|
|
• T cells constitutively express high levels of IL-17A
• this secretion is greatly enhanced after T cell stimulation
|
|
• immunization with MOG peptide plus adjuvant leads a highly significant increase in serum IL-17A levels
|
|
• there is a minor but significant increase in the number of granulocytes in the blood
|
|
• increased numbers of neutrophils are recruited into the spleen compared to controls after immunization with MOG peptide
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no cardiac phenotype under baseline conditions
|
|
• at 4 weeks after transverse aortic constriction (TAC) cardiac hypertrophy is suppressed and cardiac function is preserved compared to similarly treated wild-type controls
• cardiac function is preserved and no signs of left ventricular dilation are seen after 10 weeks of TAC unlike in controls
|
|
• at 4 weeks after transverse aortic constriction (TAC) cardiac hypertrophy is suppressed and cardiac function is preserved compared to similarly treated wild-type controls
• cardiac function is preserved and no signs of left ventricular dilation are seen after 10 weeks of TAC unlike in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hyperresponsive to stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• hyperresponsive to stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hyperresponsive to stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• hyperresponsive to stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• rare areas in prostate show outlier levels of androgen receptor expression and rare cells show cytologic atypia with enlarged nuclei in mice older than 12 months
• however, mice show minimal alterations in prostate grandular architecture and histology, no differences in proliferation or androgen receptor expression
|
|
|
• rare areas in prostate show outlier levels of androgen receptor expression and rare cells show cytologic atypia with enlarged nuclei in mice older than 12 months
• however, mice show minimal alterations in prostate grandular architecture and histology, no differences in proliferation or androgen receptor expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
• preneoplastic nodules are first detected at about 160 days of age in males
|
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased incidence of intraepithelial neoplasias in the small and large intestines
|
|
• adenomas are seen in the small and large intestines
|
|
• increased incidence of intraepithelial neoplasias in the small and large intestines
|
|
• adenomas are seen in the small and large intestines
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased incidence of intraepithelial neoplasias in the small and large intestines
|
|
• adenomas are seen in the small and large intestines
|
|
• increased incidence of intraepithelial neoplasias in the small and large intestines
|
|
• adenomas are seen in the small and large intestines
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal body composition
|
| N |
• mice exhibit normal energy homeostasis, insulin signaling and glucose homeostasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• males fed a high-fat diet (HFD) for 14 weeks (to induce obesity) show a significantly lower testicular expression of BAX and cleaved-caspase-3 protein than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly higher sperm forward motility (%) than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly higher sperm motility (%) than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly higher caudal epididymal sperm concentration than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a less distorted arrangement of germ cells in the seminiferous tubules, a better Johnsen's score, and a significantly lower teratozoospermic ratio than HFD-fed wild-type males, indicating protection from HFD/obesity-induced spermatogenic defects
|
|
|
• males fed a high-fat diet (HFD) for 14 weeks (to induce obesity) show a significantly lower testicular expression of BAX and cleaved-caspase-3 protein than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly higher sperm forward motility (%) than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly higher sperm motility (%) than HFD-fed wild-type males
|
|
|
• males fed a HFD for 14 weeks show a significantly lower number of gammaH2AX+ germ cells per seminiferous tubule than HFD-fed wild-type males, indicating protection from HFD-induced oxidative damage
|
|
|
• males fed a HFD for 14 weeks show improved testicular redox imbalance with a significantly higher NADPH/NADP ratio and significantly lower malondialdehyde (MDA) and protein carbonyls in the testes than HFD-fed wild-type males, indicating protection from HFD-induced oxidative stress
|
|
|
• males fed a HFD for 14 weeks show a significantly lower number of gammaH2AX+ germ cells per seminiferous tubule than HFD-fed wild-type males, indicating protection from HFD-induced oxidative damage
|
|
|
• males fed a HFD for 14 weeks show significantly lower malondialdehyde (MDA) levels in the testes than HFD-fed wild-type males
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in diphtheria toxin-treated mice when a high-fat diet or a low-fat diet
|
|
• in diphtheria toxin-treated mice fed a high-fat or low-fat diet
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice fed a high-fat or low-fat diet
|
|
• in diphtheria toxin-treated mice fed a low-fat during the nocturnal phase or when mice are fed a high-fat diet
|
|
• in diphtheria toxin-treated mice fed a low-fat during the nocturnal phase
|
|
• in diphtheria toxin-treated mice fed a low-fat
|
|
• in diphtheria toxin-treated mice when fed standard chow
• in diphtheria toxin-treated mice when fed a high-fat diet or a low-fat diet during an insulin tolerance test
|
|
• in diphtheria toxin-treated mice fed a high-fat
|
|
• in diphtheria toxin-treated mice when fed standard chow, a high-fat diet, or a low-fat diet
|
|
• in diphtheria toxin-treated mice fed a high-fat
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice fed standard chow or a high fat diet
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice fed a high fat diet
|
|
• in diphtheria toxin-treated mice fed a high-fat
|
|
• in diphtheria toxin-treated mice fed standard chow or a high fat diet
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice
|
|
• in diphtheria toxin-treated mice fed a low-fat
|
|
• in diphtheria toxin-treated mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| isolated growth hormone deficiency | DOID:0060870 | J:169459 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• expression of the mutant foxo1 restores body weight, food consumption and blood glucose levels to normal
|
|
• mutants have reduced basal and stress-induced corticosterone levels, similar to double Pdk1tm1Jcbr Tg(Pomc1-cre)16Lowl mutants
|
|
• same reduction in corticotrophs as seen in double Pdk1tm1Jcbr Tg(Pomc1-cre)16Lowl mutants
|
|
• same reduction in corticotrophs as seen in double Pdk1tm1Jcbr Tg(Pomc1-cre)16Lowl mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• prostate weight is similar to control
• prostate histology is similar to control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no significant differences are detected in sympathetic axon guidance; axon guidance to the submandibular gland is similar in mutants and controls
|
|
• (lacZ-labeled) mutant neurons have fewer primary dendrites compared to controls in the superior cervical ganglion (SCG) and stellate ganglion; labeled neurons have decreased total dendrite length and decrease in maximum extent of the dendritic arbor in the SCG
• neurons are significantly atrophic compared with control (decreased mean soma area)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased left ventricular internal dimension at end-diastole (LVIDd) and at systole (LVIDs)
|
|
• decreased ejection fraction (EF) and fractional shortening (FS)
|
|
• increased resting intracellular Ca2+ level in cardiomyocytes
|
|
• decreased ejection fraction (EF) and fractional shortening (FS)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 64 days
|
|
• in diseased mice
|
|
• lymphoid infiltration in the thymus at 6 months
|
|
• in diseased mice
|
|
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months
|
|
• nearly all B cells are arrested in the early pro-B stage
|
|
• in the thymus
|
|
• in the spleen
|
|
• at 6 months
|
|
• in the thymus
|
|
• immature single positive cells in the thymus
|
|
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months
|
|
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months
|
|
• in diseased mice
|
|
• lymphoid infiltration in the spleen, interstitial and perivascular space of the kidney, perivascular cuffs in the liver, meninges surrounding the brain, thymus, stomach and intestine at 6 months
|
|
• lymphoid infiltration in the intestine at 6 months
|
|
• lymphoid infiltration in the stomach at 6 months
|
|
• lymphoid infiltration in the meninges surrounding the brain at 6 months
|
|
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months
|
|
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months
|
|
• lymphoid infiltration in the intestine at 6 months
|
|
• lymphoid infiltration in the stomach at 6 months
|
|
• mice rapidly develop and succumb to acute leukemia
|
|
• in diseased mice
|
|
• in diseased mice
|
|
• in diseased mice
|
|
• in diseased mice
|
|
• in diseased mice
|
|
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months
|
|
• lymphoid infiltration in the meninges surrounding the brain at 6 months
|
|
• in diseased mice
|
|
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months
|
|
• in diseased mice
|
|
• lymphoid infiltration in the thymus at 6 months
|
|
• in diseased mice
|
|
• severely at 6 months
|
|
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months
|
|
• nearly all B cells are arrested in the early pro-B stage
|
|
• in the thymus
|
|
• in the spleen
|
|
• at 6 months
|
|
• in the thymus
|
|
• immature single positive cells in the thymus
|
|
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months
|
|
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months
|
|
• in diseased mice
|
|
• lymphoid infiltration in the thymus at 6 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• femur lengths are slightly, but significantly, reduced in 3-month-old males but not in females
|
|
|
• tibia lengths are slightly, but significantly, reduced in 3-month-old males but not females
|
|
|
• tibia bone mineral density is reduced in males but not females
|
|
|
• femur bone mineral density is reduced in males but not females
|
|
|
• femur lengths are slightly, but significantly, reduced in 3-month-old males but not in females
|
|
|
• tibia lengths are slightly, but significantly, reduced in 3-month-old males but not females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced in CD19+ B cells isolated from tamoxifen-treated mice and treated with IL4 and LPS, LPS, or IL4 and alphaCD40
|
|
• in CD19+ B cells isolated from tamoxifen-treated mice and treated with IL4 and LPS, LPS, or IL4 and alphaCD40
|
|
• reduced in CD19+ B cells isolated from tamoxifen-treated mice and treated with IL4 and LPS, LPS, or IL4 and alphaCD40
|
|
• in CD19+ B cells isolated from tamoxifen-treated mice and treated with IL4 and LPS, LPS, or IL4 and alphaCD40
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median lifespan of 40 days
|
|
|
• net volume and ratio of fat mass is lower
|
|
• adults (2 months of age) appear smaller, with decreased size beginning at 3 weeks after birth
• body weight of 2 month old males is about 35% lower than in controls
|
|
• skeletal muscle shows dilated endoplasmic reticulum lumen, reduced mitochondrial cristae density, and ruffled nucleus morphology
|
|
• reduction in muscle cross-sectional area of the soleus muscle
|
|
• increase in the prevalence of central nuclei in the myofibrils of the soleus muscle
|
|
• reduction in muscle mass
|
|
|
• net volume and ratio of fat mass is lower
|
|
|
• cell volume of white adipose tissue is lower
• however, histology of brown adipose tissue is unaffected and lean mass is unaffected
|
|
|
• frequency of twitching is increased
|
|
|
• 50% reduction in grip strength
|
|
|
• mice show reductions in the frequencies of drinking, hanging, rearing and walking during the night indicating that mice are less active at night
• however, no differences in daytime activity are seen
|
|
• nuclear morphology of skeletal muscle becomes ruffled
|
|
• endoplasmic reticulum lumen in the myonuclei is dilated
|
|
• density of mitochondrial cristae is reduced is skeletal muscle
|
|
• marker analysis indicates elevated ER stress in skeletal muscle
|
|
|
• surface temperature of the eye and the trunk is lower indicating lower body temperature
|
|
|
• carbon dioxide production per unit activity is lower during the night
|
|
|
• whole-body consumption of oxygen is lower during the night
|
|
|
• the respiratory exchange ratio is increased during the day
|
|
|
• heat production is lower at night but not during the day
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with RU486 prior to diphtheria toxin injection exhibit reduced proliferation and atrophy in the esophageal epithelia compared with wild-type mice
|
|
• mice treated with RU486 prior to diphtheria toxin injection exhibit reduced proliferation and atrophy in the esophageal epithelia compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of 108 days
• 100% of mice succumb of multiorgan failure due to extreme leukocytosis
|
|
• mice show signs of hematological disease between 30 and 90 days after birth, developing a myeloproliferative neoplasm (MPN) disease characterized by myelofibrosis, megakaryocytic-restricted dysplasia, marked mature leukocytosis, and progressive splenomegaly
|
|
• bone marrow shows an expansion of common myeloid progenitors (CMPs)
|
|
• clusters of variably segmented myeloid cells accumulate in the liver and in the red pulp of the spleen indicating extramedullary hematopoiesis
|
|
• anemia is exacerbated in lethally irradiated syngenic recipients receiving bone marrow cells from mutant doners and transplanted mice die within 16 days after transplant because of extreme anemia
• mild anemia is seen in sublethally irradiated syngenic recipients receiving bone marrow cells from mutant doners and all transplanted mice develop an accelerated form of chronic myeloproliferation
|
|
• bone marrow shows an expansion of lineage-negative (Lin-) cells
|
|
• atypical megakaryocytes are commonly seen in the bone marrow, with frequent hypolobulated bulbous nuclei, dark chromatin with irregular borders, and folding of the nuclear surface
|
|
• peripheral blood shows lower platelet counts
• thrombocytopenia is exacerbated in lethally irradiated syngenic recipients receiving bone marrow cells from mutant doners
|
|
• 100% of mice succumb of multiorgan failure due to extreme leukocytosis
• massive leukocytosis is seen in sublethally irradiated syngenic recipients receiving bone marrow cells from mutant doners and all transplanted mice develop an accelerated form of chronic myeloproliferation
|
|
• peripheral blood shows an imbalance between the lymphoid and myeloid lineages in favor of the latter, with an increase of mature myeloid cells and a reduction in the percentage of lymphocytes
• -however, no evidence of granulocytic dysplasia is seen and no circulating blasts or nonsegmented myeloid precursors are seen in the peripheral blood
|
|
• bone marrow shows overt myeloid hyperplasia with no evidence of dysplasia except for the megakaryotic lineage
|
|
• within the Lin- population, the fraction of multipotent Lin-/Sca1+/c-Kit+ (LSK) cells is reduced and very few hematopoietic stem cells (HSCs; CD150+/CD48-) are seen
• however, no change in the MPP fraction (CD150-/CD48+) is seen
|
|
• spleen shows distortion of the normal architecture
• spleen shows massive infiltration by mature myeloid cells and a loss of lymphoid cells
• spleen shows an aberrantly large Lin- population, with a significant fraction being c-Kit+/Sca1-, suggesting a myeloid progenitor phenotype
|
|
• bone marrow shows overt myeloid hyperplasia with no evidence of dysplasia except for the megakaryotic lineage
|
|
• 100% of mice succumb of multiorgan failure due to extreme leukocytosis
• massive leukocytosis is seen in sublethally irradiated syngenic recipients receiving bone marrow cells from mutant doners and all transplanted mice develop an accelerated form of chronic myeloproliferation
|
|
• spleen shows distortion of the normal architecture
• spleen shows massive infiltration by mature myeloid cells and a loss of lymphoid cells
• spleen shows an aberrantly large Lin- population, with a significant fraction being c-Kit+/Sca1-, suggesting a myeloid progenitor phenotype
|
|
• liver shows distortion of the normal architecture
|
|
• adult mice show stromal changes with reticulin fibrosis in the bone marrow
• bone marrow shows an increased network of reticulin fibers with many intersections, with a predominant peritrabecular distribution but also extending within the intertrabecular spaces, and the presence of thick, confluent collagen fibers
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| myelofibrosis | DOID:4971 |
OMIM:254450 |
J:363041 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• neural progenitor cells treated with tamoxifen exhibit increased binucleated and pyknotic cells compared with controls
• slightly increase in the number of binucleated mouse embryonic fibroblasts treated with tamoxifen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment
|
|
• tamoxifen treatment at E7.5 results in axial turning defects in most mice at E9.5
|
|
• tamoxifen treatment at E6.5 reproduces the gross phenotypes seen in germline null mice
|
|
• loss of branchial arches following tamoxifen treatment
|
|
• decrease in cephalic mesoderm at E10 in embryos treated with tamoxifen at E8.0
|
|
• tamoxifen treatment at E6.5 results in collapse of the mesenchyme
|
|
• vascular disintegration following tamoxifen treatment
|
|
• at E10 in embryos treated with tamoxifen at E8.0
|
|
• in MEFs tamoxifen treatment results in an accumulation of cells in G1/G0 and loss of S-phase and mitotic cells
|
|
• in pharyngeal mesodermal cells at E10, 48h past tamoxifen treatment
• however mitotic indices in branchial arch, neural tube, and heart cells are similar to controls
|
|
• following tamoxifen treatment
|
|
• reduced MEF cell growth following tamoxifen treatment
• however, tamoxifen treatment of embryonic stem cells does not alter cell growth
|
|
• loss of branchial arches following tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hematopoietic cells from tamoxifen-treated mice are more sensitive to gamma-irradiation compared with control cells
|
|
• hematopoietic cells from tamoxifen-treated mice are more sensitive to gamma-irradiation compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected mice are observed at P10
|
|
• disturbed hematopoietic development in adult hematopoietic progenitor cells
|
|
• reduced total number of colony forming units from bone marrow cells
|
|
• in bone marrow cells
|
|
• in bone marrow cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit no obvious phenotype and normal vasculature at E11.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are obtained in normal Mendelian ratios
|
| N |
• at E10.5, mice exhibit no enhancement of endothelial cells
|
| N |
• at E10.5, mice exhibit no enhancement of hematopoietic progenitor cells
|
| N |
• mice develop without phenotypic abnormalities during embryogenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Retardation of retinal vascular growth in Gt(ROSA)26Sortm1(CAG-Rhoj,-EGFP)Auem/Gt(ROSA)26Sor+ Tg(Tek-cre)2352Rwng/0 mice
|
• retinal vascular growth retardation (reduced radial extension) at P4
|
|
• retinal vascular growth retardation (reduced radial extension) at P4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within days of tamoxifen-induction
|
|
• following tamoxifen-induction, mucosal epithelial cells of the mucosae of the stomach and the small and large intestines exhibit widespread degeneration and necrosis compared with control mice
|
|
• distended and filled with yellowish clear fluid following tamoxifen-induction
|
|
• following tamoxifen-induction, mice exhibit mucosal epithelial degeneration of cecal mucosa compared with control mice
|
|
• following tamoxifen-induction, mice exhibit mucosal epithelial degeneration of duodenal mucosa compared with control mice
|
|
• following tamoxifen-induction, mice exhibit ulceration of nonglandular mucosa and parietal cell degeneration of glandular mucosa compared with control mice
|
|
• parietal cell degeneration of glandular mucosa following tamoxifen-induction
|
|
• distended and filled with food following tamoxifen-induction
|
|
• parietal cell degeneration of glandular mucosa following tamoxifen-induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within 10 to 11 days of tamoxifen-induction
|
|
• following tamoxifen-induction, mice exhibit widespread mucosal epithelial degeneration more so in the small and large intestines and less in the stomach compared with control mice
• however, mice do not exhibit a distended intestine morphology
|
|
• focal atypical hyperplasia of mucosal crypts with small clusters of enlarged atypical crypts lined by tall dysplastic basophilic epithelial cells in the small intestine following tamoxifen-induction
|
|
• following tamoxifen-induction, mice exhibit swollen and basophilic surface epithelial cells in the large intestine compared with control mice
|
|
• loss of mucosal crypts in some areas of the large intestine following tamoxifen-induction
|
|
• following tamoxifen-induction, mice exhibit swollen villous epithelial cells with excessive vacuoles in the small intestine compared with control mice
|
|
• following tamoxifen-induction, mice exhibit loose or discolored intestine content
|
|
• thin following tamoxifen-treatment
|
|
• in moribund mice following tamoxifen-induction
|
|
• following tamoxifen-treatment
|
|
• poor coat condition following tamoxifen-treatment
|
|
• loss of mucosal crypts in some areas of the large intestine following tamoxifen-induction
|
|
• focal atypical hyperplasia of mucosal crypts with small clusters of enlarged atypical crypts lined by tall dysplastic basophilic epithelial cells in the small intestine following tamoxifen-induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with tamoxifen exhibit degeneration of intestinal crypts
|
|
• mice treated with tamoxifen exhibit villous blunting
|
|
• mice treated with tamoxifen exhibit villous fusion
|
|
• mice treated with tamoxifen exhibit segmental, submucosal edema in the large intestine
|
|
• mice treated with tamoxifen exhibit increased apoptosis in the small intestine
|
|
• mice treated with tamoxifen exhibit mild enteritis
|
|
• mice treated with tamoxifen exhibit degeneration of intestinal crypts
|
|
• mice treated with tamoxifen show thymic atrophy
|
|
• mice treated with tamoxifen lose between 13 and 28% of their body weight after 6 to 7 days
|
|
• mice treated with tamoxifen show thymic atrophy
|
|
• mice treated with tamoxifen exhibit pyknotic and karyorrhectic lymphocytes in secondary lymphoid organs
|
|
• mice treated with tamoxifen exhibit segmental, submucosal edema in the large intestine
|
|
• mice treated with tamoxifen exhibit mild enteritis
|
|
• mice treated with tamoxifen show thymic atrophy
|
|
• mice treated with tamoxifen exhibit pyknotic and karyorrhectic lymphocytes in secondary lymphoid organs
|
| N |
• mice treated with tamoxifen do not show signs of morbidity after 5 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 12 days following tamoxifen-treatment in male mice
• however, female mice remain normal
|
|
|
• following tamoxifen-treatment, male mice exhibit similar observations as in homozygous conditional knock-ins but with lower severity
|
|
|
• following tamoxifen-treatment in male mice
• however, female mice remain normal
|
|
|
• following tamoxifen-treatment in male mice
• however, female mice remain normal
|
|
|
• following tamoxifen-treatment, one female mouse exhibited a black focal mild discoloration of the spleen
|
|
|
• poor coat condition following tamoxifen-treatment in male mice
• however, female mice remain normal
|
|
|
• following tamoxifen-treatment, one female mouse exhibited a black focal mild discoloration of the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• upon aging, all mice develop a hematopoietic malignancy with a median survival of 186 days
|
|
• leukemic mice show reduced body weight
|
|
• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments
|
|
• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments
|
|
• bone marrow of 8-week-old mice shows reduced numbers of erythroid (Ter119+) and NK cells (CD3-NK1.1+) and increased numbers of T cells (CD3+CD4+ or CD3+CD8+)
|
|
• 8-week-old mice exhibit elevated bone marrow cellularity
|
|
• numbers of erythroid (Ter119+) cells are reduced in the bone marrow of 8-week-old mice
|
|
• numbers of NK cells (CD3-NK1.1+) are reduced in the bone marrow of 8-week-old mice
|
|
• peripheral blood lacks any significant alterations, except for a decrease in the frequency of CD4+ T cells
|
|
• mice show elevated numbers of mature hematopoietic cell types in spleen, blood, and lymph nodes, but not in the bone marrow
• cell numbers are elevated in all lineages and no cell type is dominantly expanded
|
|
• numbers of B cells (CD19+) are increased in the bone marrow of 8-week-old mice
|
|
• numbers of T cells (CD3+CD4+ or CD3+CD8+) are increased in the bone marrow of 8-week-old mice
|
|
• 8-week-old mice exhibit an enlarged hematopoietic stem cell pool under homeostatic conditions
|
|
• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments
|
|
• numbers of B cells (CD19+) are increased in the bone marrow of 8-week-old mice
|
|
• numbers of NK cells (CD3-NK1.1+) are reduced in the bone marrow of 8-week-old mice
|
|
• peripheral blood lacks any significant alterations, except for a decrease in the frequency of CD4+ T cells
|
|
• numbers of T cells (CD3+CD4+ or CD3+CD8+) are increased in the bone marrow of 8-week-old mice
|
|
• mice develop slowly progressing CD4+, CD8+ T- or NKT-cell leukemia, as indicated by blood smears of diseased mice which show leukemic blast-like cells
• leukemic T/NKT cells expand upon transplantation into immunodeficient NOD scid gamma (NSG) recipients, infiltrating the bone marrow, spleen and lungs indicating the development of leukemia
• however, mice do not develop NK-cell leukemia
• mice show immune cell infiltration in the lungs which is associated with disruption of the regular lung architecture
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 4 and 8 weeks after tamoxifen treatment, neurons exhibit a progressive reduction of spine density in the stratum radiatum compared with control neurons
• tamoxifen-treated neurons exhibit a decreased fraction of mushroom type spines and increased filopodia-like spines compared with control neurons
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• brain size, myelination, and oligodendrocyte numbers are similar to controls unlike in mutant mice without the knock-in allele in Gt(ROSA)26Sor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos are viable at E14.5 but with severe limb deformities
|
|
• severe limb deformities at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in an amphetamine (1, 3 or 5 mg/kg) conditioned place preference (CPP) paradigm in mice with NAc deletion of dopamine receptor 2 (D2R)-specific striatopallidal neurons, analysis of the extinction of CPP over 1 week showed that mutants maintained greater CPP on days 4 and 9 after last amphetamine injection whereas controls showed loss of CPP on day 9
|
|
• at 6 days after bilateral full striatum diptheria toxin injection, mice show 3 to 4-fold higher activity in the open field; hyperactivity is stable through 16 days post-injection, with hyperactivity still apparent at 33 days
• however, deletion of D2R-striatopallidal neurons in the nucleus accumbens (NAc) by injection of diptheria toxin does not result in spontaneous hyperlocomotion in the mice
|
| N |
• mesostriatal dopaminergic system after ablation of striatopallidal neurons by diptheria toxin injection was not significantly different from controls in terms of dopamine extracellular concentration or amphetamine-induced dopamine overflow
|
|
• unilateral or bilateral diptheria toxin injection into the striatum causes unilateral or complete loss of dopamine receptor 2 (D2R)-specific striatopallidal neurons at 14 days after injection; neuron loss was similar from the anterior to the posterior striatum
• dopamine receptor 1-specific neurons are unaffected and striatal interneuron populations remain intact
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• electroneurogram recordings from ventral roots indicates a suppression of synaptic transmission disrupting locomotor rhythm
• outputs from spinal cords show increased variability in the duration of individual motor bursts and in the length of the step cycle period which may be coupled with asymmetry in the duration of flexor bursts between the right and left sides of the spinal cord
• spinal cords show impaired production of locomotor like oscillations following induction with NMDA and 5-hydroxytryptamine or after electrical stimulation of sensory afferents
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• block of synaptic transmission between spinal neurons that is necessary for fictive locomotion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and express LacZ in cells where cre is expressed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and express LacZ in cells where cre is expressed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit a decrease in hind limb footprint length that is similar to the pes cavus foot deformity in humans
|
|
|
• diminished number of mitochondria in peripheral nerve axons, with fewer mitochondria per tibial axon
• however, no mitochondrial aggregation is seen
|
|
|
• soleus muscle shows evidence of peripheral satellite cell fusion with soleus muscle fibers
• both small angulated myofibers and fiber grouping is absent in the soleus muscle
|
|
|
• soleus muscle exhibits a decrease in sarcomeric actin immunostaining and disruption of the normal striatal mitochondrial organization
|
|
|
• fast muscle fiber diameter of the tibialis and slow/mixed muscle fiber diameter of the soleus are reduced
|
|
|
• fast muscle fiber atrophy in the anterior tibialis musculature
• myofiber atrophy in soleus muscle
|
|
|
• conversion of slow to mixed slow/fast fibers
|
|
N |
• no abnormal myelination is seen and the number of myelinating axons, their diameters, and degree of myelination in sciatic nerve is normal
|
|
|
• soleus muscle shows evidence of peripheral satellite cell fusion with soleus muscle fibers
• both small angulated myofibers and fiber grouping is absent in the soleus muscle
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Charcot-Marie-Tooth disease type 2A2A | DOID:0110155 |
OMIM:609260 |
J:251584 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cortical sulci and gyri in newborn (P0) mice
|
|
• increased subventricular zone (SVZ) in E15.5 embryos
• two-fold increase (15% to 30%) in number of Pax6+ neural progenitor (NP) cells in SVZ
• significant increase in Pax6+ outer radial glia (oRG) cells visualized by phospho-Vimentin staining in SVZ
• increase in Sox2+ and Tbr2+ intermediate progenitor (IP) cells in SVZ
• increased proliferation and shortened cell cycle of NP cells in SVZ
• doubling of oblique cell divisions (14% to 28%) of ventricular radial glia (vRG) cells in SVZ
|
|
• thickened in P0 mice
|
|
• in newborn (P0) mice
• increased cortical area, volume and perimeter, anterior-posterior and mediolateral size
|
|
• increased proliferation and shortened cell cycle of NP cells in SVZ
• doubling of oblique cell divisions (14% to 28%) of ventricular radial glia (vRG) cells in subventricular zone (SVZ)
• cortical sulci and gyri in newborn (P0) mice
• proliferation of NP cells in ventricular zone (VZ)
• increase in Sox2+ and Tbr2+ intermediate progenitor (IP) cells in SVZ
• significant increase in Pax6+ outer radial glia (oRG) cells visualized by phospho-Vimentin staining in SVZ
• Pax6+ progenitor cells expanded radially toward intermediate zone (IZ)
• two-fold increase (15% to 30%) in number of Pax6+ neural progenitor (NP) cells in SVZ
• age E15.5 embryos
|
|
• thickening due to increased subventricular zone (SVZ) in E15.5 embryos
• thickened cortical plate (CP) in P0 mice
• increase in Satb2+ (upper layer II/III marker) cells in P0 mice
• increase in Ctip2+ (deep layer V marker) cells in P0 mice
• increase in Foxp2+ (deep layer VI marker) cells in P0 mice
|
|
• in newborn (P0) mice
• increased cortical area, volume and perimeter, anterior-posterior and mediolateral size
|
|
• increased subventricular zone (SVZ) in E15.5 embryos
• two-fold increase (15% to 30%) in number of Pax6+ neural progenitor (NP) cells
• significant increase in Pax6+ outer radial glia (oRG) cells visualized by phospho-Vimentin staining
• increase in Sox2+ and Tbr2+ intermediate progenitor (IP) cells
• increased proliferation and shortened cell cycle of NP cells
• doubling of oblique cell divisions (14% to 28%) of ventricular radial glia (vRG) cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups are stillborn and small
• pups develop until almost full term (E19.5)
|
|
• E16.5 embryos exhibit deformed limbs
|
|
• observed in E16.5 embryos
|
|
• E16.5 embryos exhibit aberrant spinal columns
|
|
• E16.5 embryos exhibit underdeveloped rib cages
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E16.5 display a much thicker bone collar and no bone marrow
|
|
• at E16.5 the marrow region is occupied by cells that appear to be preosteoblasts and no marrow cavity is formed
• at E18.5 the marrow region is populated by mature osteoblasts
|
|
• profoundly dense bones throughout the body at 2 months of age
|
|
• at E18.5 the marrow region is populated by mature osteoblasts
|
|
• at E18.5 and 2 months of age
• when cre expression is suppressed by doxycycline treatment until 1 month of age mice show a profound high bone mass phenotype at 2 months of age
|
|
• slight delay in chondrocyte maturation at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• keratin cyst formation is observed
|
|
• generalized growth retardation is observed compared to controls
|
|
• mice develop spontaneous cutaneous SCC lesions, as well as dysplastic precursor lesions
|
|
• with aging, hyperkeratinization of tail is seen
|
|
• aberrant hair follicle cycling occurs
|
|
• starting at 2-3 weeks, mice display hair and whisker loss; diffuse alopecia is observed
• at 10 months of age, alopecia has progressed almost to completion
|
|
• hypoplastic dermis with increased cellularity is observed
• by 6 months of age, most mice develop hyperkeratotic cutaneous nodules, with all mutants exhibiting multiple lesions by 10 months of age
• examination of some nodules reveals papillomas or inflamed infundibular cyts
|
|
• keratin cyst formation is observed
|
|
• cutaneous nodules show hyperproliferative keratinocytic lesions exhibiting cellular atypia and an invasive growth pattern
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• long bone osteoblasts exhibit an increased expression of inflammatory cytokines during osteoblast differentiation
|
|
• osteoclast number is increased in lumbar vertebral bodies and tibiae and osteoclast-covered surface of lumbar vertebral bodies and tibiae is increased in males
• osteoclast surface per bone surface and osteoclast number per bone perimeter is increased in vertebral bodies of females
• however, no differences in osteoblast-covered surface or number are seen
|
|
• femurs exhibit a smaller midshaft diameter
|
|
|
• tibia show decreased midshaft diameter
|
|
• decrease in trabecular bone volume in femurs and lumbar spine of males
• decrease in trabecular bone volume in lumbar spine of females
|
|
|
• femurs show decreased cortical porosity
|
|
• femurs and tibiae show an increase in cortical thickness
|
|
• decrease in trabecula number in femurs and lumbar spine of males
• decrease in trabecula number in lumbar spine of females
|
|
|
• increase in trabecular separation in femurs and lumbar spine
|
|
|
• decrease in trabecular bone connection density
|
|
• femurs show decreased trabecular mass
|
|
|
• reduction in cortical mineralization of femurs
|
|
• tibial endocortical bone surface shows an increase in endosteal mineralizing surface
|
|
|
• tibial endocortical bone surface shows an increase in endosteal bone formation rate
• however, no differences in periosteal or trabecular bone formation parameters
|
|
|
• the elastic modulus and work to reach ultimate stress levels are lower in femurs, indicating that femurs tolerate higher stress levels and are more elastic/flexible
|
|
|
• two mice exhibit fracture with callus in the tibia
• femurs bear higher stress levels in the three-point bending tests but work-to-fracture is 42% lower
|
|
|
• long bone osteoblasts exhibit an increased expression of inflammatory cytokines during osteoblast differentiation
|
|
• osteoclast number is increased in lumbar vertebral bodies and tibiae and osteoclast-covered surface of lumbar vertebral bodies and tibiae is increased in males
• osteoclast surface per bone surface and osteoclast number per bone perimeter is increased in vertebral bodies of females
• however, no differences in osteoblast-covered surface or number are seen
|
|
• osteoclast number is increased in lumbar vertebral bodies and tibiae and osteoclast-covered surface of lumbar vertebral bodies and tibiae is increased in males
• osteoclast surface per bone surface and osteoclast number per bone perimeter is increased in vertebral bodies of females
• however, no differences in osteoblast-covered surface or number are seen
|
|
• femurs and tibiae show an increase in cortical thickness
|
|
• femurs exhibit a smaller midshaft diameter
|
|
|
• tibia show decreased midshaft diameter
|
| N |
• mice exhibit normal calvarial bone thickness and porosity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• proximal tibial trabecular bone volume/total volume is increased 13.7 fold and 5.1 fold at 2 months and 6 months of age, respectively
• by 9 months of age bone mass of the proximal tibial trabecular area is 30% less than controls
|
|
• osteoclast number per bone surface and percentage of bone resorption surface are reduced at 2 months of age
|
|
• absence of a marrow space in the long bones due to complete ossification
|
|
• profoundly dense bones in both males and females throughout the body at 2 months of age
• increased density persists at 6 months of age but is partially resolved at 9 months of age
|
|
• by 9 months of age bone mass of the proximal tibial trabecular area is 30% less than controls
• however, bone mass remains increased in the distal tibia and femur at 9 months of age
|
|
• proximal tibial trabecular bone volume/total volume is increased 13.7 fold and 5.1 fold at 2 months and 6 months of age, respectively
|
|
• excessive osteoblasts in the presumptive marrow cavity at E18.5
• increased osteoblast number normalized to bone surface at 2 months of age
• however, the density of osteocytes is similar to controls
|
|
• excessive bone occupies both primary and secondary ossification centers but the growth plate remains largely normal
• increased bone mass is seen at E18.5 and at 2 and 6 months of age
|
|
• mineral apposition rate, the percentage of mineralizing surface, and bone formation rate are all increased in the humerus
|
|
• increase in the serum levels of C-terminal telopeptide of type I collagen (a degradation product of type I collagen released upon bone resorption) at 1 and 9 months of age but not at 2 months of age
|
|
• increased at 1 and 2 months of age
|
|
• increase in the serum levels of C-terminal telopeptide of type I collagen (a degradation product of type I collagen released upon bone resorption) at 1 and 9 months of age but not at 2 months of age
|
|
• consistent with extramedullary hematopoiesis
|
|
• osteoclast number per bone surface and percentage of bone resorption surface are reduced at 2 months of age
|
|
• consistent with extramedullary hematopoiesis
|
|
• osteoclast number per bone surface and percentage of bone resorption surface are reduced at 2 months of age
|
|
• proximal tibial trabecular bone volume/total volume is increased 13.7 fold and 5.1 fold at 2 months and 6 months of age, respectively
• by 9 months of age bone mass of the proximal tibial trabecular area is 30% less than controls
|
|
• consistent with extramedullary hematopoiesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• administration of doxycycline to pregnant dam starting at day E1.5 and consequent VEGF-A164 expression in neural cell lineage caused vascular abnormalities by E12.5 associated with spinal cord and brain hemorrhages
|
|
• administration of doxycycline to pregnant dam starting at day E1.5 and consequent VEGF-A164 expression in neural cell lineage caused vascular abnormalities by E12.5 associated with spinal cord and brain hemorrhages
|
|
• administration of doxycycline to pregnant dam starting at day E1.5 and consequent VEGF-A164 expression in neural cell lineage caused vascular abnormalities by E12.5 associated with spinal cord and brain hemorrhages
|
|
• administration of doxycycline to pregnant dam starting at day E1.5 and consequent VEGF-A164 expression in neural cell lineage caused vascular abnormalities by E12.5 associated with spinal cord and brain hemorrhages
|
| N |
• administration of doxycycline in the drinking water to 3-4 month old mice and consequent VEGF-A164 expression in neural cell lineage did not cause obvious gross behavioral or phenotypic abnormalities in brain after 5 days of treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• normal outflow tract septation in E9.5 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• in E16 and E17 embryos
|
|
• mandibular cleft in E14-E17 embryos
|
|
• in E17 embryos
|
|
• in E16 and E17 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a partial depletion of the progenitor zone in the neural tube of E12.5 embryos
• there is a minor decrease of under 10% in the number of dILB neurons found in embryos
|
|
• mice exhibit a decrease in dILB neurons
|
|
• the progenitor domain is reduced compared to in wild-type mice
|
|
• there is a partial depletion of the progenitor zone in the neural tube of E12.5 embryos
• there is a minor decrease of under 10% in the number of dILB neurons found in embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• although tamoxifen-treated mice show trends towards changes in the Morris Water maze, they are not significant
|
|
N |
• although tamoxifen-treated mice show trends towards changes in long-term potentiation (LTP) recordings, they are not significant
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal appendage development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all heterozygotes die before 5 days of age
|
|
• simple columnar epithelial cells along the esophagus at E15.5, primarily ventrally
|
|
• scattered appearance of simple columnar epithelium in the forestomach at E15.5 and at birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• diameter of collateral arteries of ischemic hindlimbs is increased in tamoxifen-treated mice
|
|
|
• the capillary density in the gastrocnemius muscles of ischemic hindlimbs is decreased in tamoxifen-treated mice
|
|
|
• tamoxifen-treated mice show increased collateral artery arteriogenesis in the hindlimb ischemia model
|
|
|
• tamoxifen-treated mice show increased blood perfusion in the ischemic hindlimbs 21 days after femoral artery ligation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when cultured on fibronectin-coated plates, inter-follicular epidermis melanocytes exhibit increased survival compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• female mice treated with ENU survive for 86 days as compared to 66-71 days for mice carrying ApcMin alone
|
|
• female mice treated with ENU develop significantly fewer intestinal tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer mammary tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer mammary or intestinal tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer mammary or intestinal tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer mammary tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer mammary tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
• female mice treated with ENU develop significantly fewer intestinal tumors than mice carrying either ApcMin alone or C57BL/6 controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mitochondria exhibit reduced levels of trimethyllysine (TML) and asymmetric dimethylarginine (ADMA) along with a decrease in saccharopine, an intermediate in lysine degradation, indicating impaired mitochondrial import of methylated amino acids
• fasted mice show a depletion of hepatic guanidinoacetate, a mitochondrial intermediate of arginine metabolism and creatine biosynthesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• delayed or incomplete clustering of microtubule-organizing centers in embryonic cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• increased motor neuron size with increased proprioceptive nerves compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• increased proprioceptive nerves in contact with motor neurons compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• at P4, P8 and P11, endplate size is increased compared to in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
• at P1, P4 and P8, endplates exhibit an increase in axon input compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice, mice exhibit impaired motor abilities in tube and righting tests compared with control mice
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased motor neuron size compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
|
|
• at P4 and P8, endplate size is increased compared to in Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• at P1 and P4, endplates exhibit an increase in axon input compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by E8.5, homozygotes appear to resorb or degenerate and lack distinct features; no mutants are detected after E8.5
|
|
• mutants are unable to show even the earliest signs of gastrulation
|
|
• homozygotes appear normal in size and morphology at the early egg cylinder stage (E6.0), but fail to develop beyond this stage
|
|
• at E6.5 and E7.5, homozygotes exhibit growth retardation relative to wild-type embryos
|
|
• up to E6.0, mutant embryos appear normal and contain embryonic and extraembryonic structures and proamniotic cavities; however, by E6.5, the simple egg cylinder fails to elongate
• homozygotes show a rapid decline of proliferative activity and elevated cell death in the epiblast at the time of egg cylinder elongation; in contrast, proliferation occurs normally prior to E6.0
|
|
• mutant embryos fail to form a histologically recognizable mesoderm at gastrulation; they fail to form mesodermal cells or express mesodermal markers
|
|
• mutant embryos contain abnormal pyknotic cells and fail to form a primitive streak
|
|
• by E6.5, mutant extraembryonic regions appear to be underdeveloped relative to wild-type; a cavitated extraembryonic region fails to form
|
|
• mutant ectoplacental cones are proportionately correct in size but degenerate after E6.5
|
|
• visceral and parietal endoderm layers are present at E6.5 and E7.5, but appear developmentally delayed and fail to form the flattened endodermal cell phenotype in the embryonic region
|
|
• visceral and parietal endoderm layers are present at E6.5 and E7.5, but appear developmentally delayed and fail to form the flattened endodermal cell phenotype in the embryonic region
|
|
• at E6.5 and E7.5, homozygotes exhibit growth retardation relative to wild-type embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 15 days of doxycycline exposure leads to CD4 induction in all but the earliest CD4- thymocytes (not in DN1-3)
• only about 30% of peripheral CD8 cells begin expressing CD4
|
|
• 15 days of doxycycline exposure leads to CD4 induction in all but the earliest CD4- thymocytes (not in DN1-3)
• only about 30% of peripheral CD8 cells begin expressing CD4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: unlike mice on a C57BL/6N background, mice on a mixed background exhibit premature death with a modest increased in mean survival compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
| N |
• unlike in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit restored synaptic vesicle area with an increase in the synaptic vesicle to endplate area ratio at P14, active zones and endplate potential electrophysiology
|
|
• mice exhibit an partial restoration of readily releasable pool and quantal content compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, small intestine mucosal epithelial cells exhibit intracytoplasmatic vacuoles at the tips of the villi and lacteals are occasionally dilated
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
|
|
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice exhibit impaired motor abilities in tube and righting tests that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
|
|
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice on a mixed background exhibit impaired righting that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice on a mixed background exhibit decreased body weight that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
• mice exhibit an partial restoration of readily releasable pool and quantal content compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination but not as severe as in mice heterozygous for Irf4tm1Mak
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination but not as severe as in mice heterozygous for Irf4tm1Mak
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination but not as severe as in mice heterozygous for Irf4tm1Mak
|
|
• doxycycline-treated mice exhibit enhanced plasma cell generation at the expense of class switch recombination but not as severe as in mice heterozygous for Irf4tm1Mak
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• >5% of caudal epididymidal sperm contain kinks in the neck
|
|
|
• >15% of caudal epididymidal sperm contain kinks in the midpiece
|
|
|
• caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles
|
|
|
• >40% of caudal epididymidal sperm contain kinks in the principal piece
|
|
|
• >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck
|
|
|
• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
|
|
|
• caudal epididymidal sperm are significantly less motile than wild-type sperm
|
|
|
• in an in vitro fertilization assay, cauda epididymidal sperm failed to fertilize any oocytes
|
|
|
• >5% of caudal epididymidal sperm contain kinks in the neck
|
|
|
• >15% of caudal epididymidal sperm contain kinks in the midpiece
|
|
|
• caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles
|
|
|
• >40% of caudal epididymidal sperm contain kinks in the principal piece
|
|
|
• >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck
|
|
|
• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
|
|
|
• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
|
|
|
• total mito-Dendra2 fluorescence is markedly reduced in the midpiece of epididymidal sperm
|
|
|
• caudal epididymidal sperm are significantly less motile than wild-type sperm
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice not supplemented with doxycycline exhibit normal embryonic survival
|
|
• at 9 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• orthotopic osteoblast differentiation is impaired as determined by marker expression
|
|
• decreased at E18.5
|
|
• the hypertrophic zone lacks vascularization unlike in wild-type mice
|
|
• columnar organization prior to hypertrophy is absent unlike in wild-type mice
|
|
• orthotopic osteoblast differentiation is impaired as determined by marker expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal kidney architecture
|
|
• doxycycline-treated mice exhibit some of segmental glomerulus basement membrane thickening observed in Col4a3tm1Jhm homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant increase in occupancy of serum transferrin with iron
|
|
• increase in liver non-heme iron levels
• this increase is intermediate between that of mice homozygous for Hfetm2Nca or Gt(ROSA)26Sortm1(Tfrc*)Nca alone
• deposition of iron is predominantly periportal
|
|
• increase in liver non-heme iron levels
• this increase is intermediate between that of mice homozygous for Hfetm2Nca or Gt(ROSA)26Sortm1(Tfrc*)Nca alone
• deposition of iron is predominantly periportal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice with doxycycline-induced ectopic Oct4 expression become morbid after 3-5 days of treatment and usually die after 5-10 days of treatment
• however, if doxycycline treatment is stopped after 5 days mice completely recover
|
|
• after doxycline treatment, dysplastic cells are found in the entire epithelium; cells have structural and cytological dysplasia which mimics adenocarcinoma
|
|
• the proximal part of the small intestine is most severely affected by doxycycline treatment with abnormal cells often almost obstructing the lumen
• after 5 days of doxycycline treatment, proliferative zone expands; postmitotic, differentiated cells lining the villus are replaced
• upon cessation of treatment, cells migrate to final destinations and differentiate resulting in restoration of normal morphology
|
|
• in doxycycline treated mice, cells in the forestomach show a marked atypia and increased mitotic activity
|
|
• pyloric mucosa contains lesions resembling high grade-dysplasia in doxycycline treated mice
|
|
• hyperplastic fundic glands are seen in doxycycline treated mice
|
|
• in doxycycline treated mice, forestomach epithelium is thickened and stomach shows lack of differentiation into granular and cornified cell layers compared to control mice
• the thickened epithelium consists of atypical cells with enlarged nuclei and prominent nucleoli
|
|
• after doxycycline treatment, mice display severe dysplasia and increased proliferation
|
|
• cells show atypia and increased mitotic activity throughout the squamous epithelial layer in doxycycline treated mice
|
|
• after 3-5 days of doxycycline treatment, animals display severe dehydration
|
|
• abnormal cell proliferation is observed in several organs after 2 days of Oct4-induction
• however, complete reversion is seen with withdrawal of doxycycline treatment
|
|
• atrophy and absence of CD4, CD8 double positive cells in doxycycline treated mice
|
|
• in doxycycline treated mice
|
|
• atrophy and absence of CD4, CD8 double positive cells in doxycycline treated mice
|
|
• in doxycycline treated mice
|
|
• in doxycycline treated mice, tumors originating from the outer-root-sheath progenitors and invading the subcutaneous layer are seen
|
|
• increased numbers of immature cells in the hair follicles of the skin are seen after 5-10 days of doxycycline
|
|
• after 5-10 days of doxycycline treatment, mice show mild to moderate epidermal dysplasia with a decrease in differentiation in dysplastic cells
|
|
• in doxycycline treated mice, tumors originating from the outer-root-sheath progenitors and invading the subcutaneous layer are seen
|
|
• hyperplastic fundic glands are seen in doxycycline treated mice
|
|
• atrophy and absence of CD4, CD8 double positive cells in doxycycline treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 3 to 10 months of doxycycline-treated mice with median survival of 20 weeks
|
|
• in doxycycline-treated mice following withdrawal of doxycycline
|
|
• in the trunks, heads, limbs, and whisker pads of all doxycycline-treated mice after 3 months arising from neural crest-lineage cells
|
|
• in doxycycline-treated mouse embryonic fibroblasts
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| clear cell sarcoma | DOID:4233 | J:194505 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when treated in utero with doxycycline, mice die shortly after birth
|
|
• doxycycline-treated mouse embryonic fibroblasts arrest in S phase with increased DNA content compared with untreated cells
|
|
• doxycycline-treated mouse embryonic fibroblasts exhibit early cellular replicative senescence compared with untreated cells
• however, withdrawal of doxcycline restores proliferation
|
|
• mice treated with doxycycline during adulthood exhibit no abnormal phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when treated in utero with doxycycline, mice die shortly after birth
|
|
• doxycycline-treated mouse embryonic fibroblasts arrest in S phase with increased DNA content compared with untreated cells
|
|
• doxycycline-treated mouse embryonic fibroblasts exhibit early cellular replicative senescence compared with untreated cells
• however, withdrawal of doxcycline restores proliferation
|
|
• mice treated with doxycycline during adulthood exhibit no abnormal phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice with lymphoma exhibit median survival or 5.3 months
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in the thymus and lymph nodes of mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• mice treated with doxycycline for 6 weeks (either initiated at birth or 4 to 6 weeks of age) exhibit excessive hair growth compared with wild-type mice
|
|
• in mice treated with doxycycline beyond 20 weeks
• however, reactivation after 4 weeks of doxycycline prevents hair loss
|
|
• in mice treated with doxycycline beyond 20 weeks
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
• reactivation after 4 weeks of doxycycline treatment does not rescue stunted snout
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
• reactivation after 4 weeks of doxycycline treatment does not rescue stunted snout
|
|
• runting in mice treated with doxycycline 1 to 2 days prior to birth
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lymphoid leukemia | DOID:1037 | J:171191 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice with lymphoma exhibit median survival of 7.4 months
|
|
• at E14.5 and E18.5, mice treated with doxycycline at E8.5 exhibit severely delayed or absent endochondral ossification of multiple skeletal elements (spine, ribs, and limbs) compared with wild-type mice
• mice transiently treated with doxycycline between E8.5 and E12.5 exhibit some reduced bone growth (ribs, spine, and skull) compared with wild-type mice
|
|
• at E14.5 and E18.5, mice treated with doxycycline at E8.5 exhibit severely delayed or absent endochondral ossification of multiple skeletal elements (spine, ribs, and limbs) compared with wild-type mice
• mice transiently treated with doxycycline between E8.5 and E12.5 exhibit some reduced bone growth (ribs, spine, and skull) compared with wild-type mice
|
|
• mice treated with doxycycline for 6 weeks (either initiated at birth or 4 to 6 weeks of age) exhibit excessive hair growth compared with wild-type mice
|
|
• in mice treated with doxycycline beyond 20 weeks
• however, reactivation after 4 weeks by doxycycline withdrawal prevents hair loss
|
|
• in mice treated with doxycycline beyond 20 weeks
|
|
• in mice treated with doxycycline at E8.5
• however, mice transiently treated with doxycycline between E8.5 and E12.5 do not exhibit edema
|
|
• mice transiently treated with doxycycline between E8.5 and E12.5 exhibit extra digits (total 5 to 9) that are largely unsegmented and duplicated along their length compared with wild-type mice
|
|
• mice transiently treated with doxycycline between E8.5 and E12.5 exhibit severely stunted hind- and forelimb development compared with wild-type mice
|
|
• mice transiently treated with doxycycline between E8.5 and E12.5 exhibit severely stunted hind- and forelimb development compared with wild-type mice
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
• reactivation after 4 weeks of doxycycline treatment does not rescue stunted snout
|
|
• runting in mice treated with doxycycline 1 to 2 days prior to birth
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
|
|
• at E14.5 and E18.5 in mice treated with doxycycline at E8.5
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in the thymus and lymph nodes of mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline 1 to 2 days prior to birth
• reactivation after 4 weeks of doxycycline treatment does not rescue stunted snout
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
• in mice treated with doxycycline from 4 to 6 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in doxycycline-treated neonates
|
|
• in doxycycline-treated neonates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline at E8.5 exhibit smaller jugular lymph sac at E 14.5 compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• periportal with immune infiltrate in doxycycline-treated mice
|
|
• in doxycycline-treated mice at necropsy
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice at necropsy
|
|
• in doxycycline-treated mice at necropsy
|
|
• in doxycycline-treated mice at necropsy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die 10 days after treatment with doxycycline
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lineage skewing is seen following short term doxycycline exposure
|
|
• develops over time
|
|
• decrease in the proportion of B cell population (B220+) develops over time
|
|
• disrupted morphology
|
|
• following short term doxycycline exposure
|
|
• develops over time
|
|
• decrease in the proportion of B cell population (B220+) develops over time
|
|
• disrupted morphology
|
|
• following short term doxycycline exposure
|
|
• following short term doxycycline exposure
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice become ill and must be euthanized 4-6 days after doxycycline treatment
|
|
• mature goblet cells are absent 5 days after doxycycline treatment
• however, the absence of mature goblet cells is reversed by doxycycline-withdrawal and administration of dipenzazepine increased goblet cell numbers
|
|
• increased proliferation of epithelium cells in the crypt regions, villus regions and at the tip of the villi of undifferentiated progenitor cells in doxycycline-treated mice
• dipenzazepine administration decreases cell proliferation in the intestine of mice treated with doxycycline
• however, proliferation of undifferentiated cells is reversed by doxycycline-withdrawal
|
|
• in doxycycline-treated mice
|
|
• severe dysplasia in doxycycline-treated mice
|
|
• Paneth cells are absent 5 days after doxycycline treatment
• however, the absence of Paneth cells is reversed by doxycycline-withdrawal
|
|
• in doxycycline-treated mice
|
|
• Paneth cells are absent 5 days after doxycycline treatment
• however, the absence of Paneth cells is reversed by doxycycline-withdrawal
|
|
• in doxycycline-treated mice
|
|
• ductal metaplasia of pancreatic acinar cells in doxycycline-treated mice
|
|
• mature goblet cells are absent 5 days after doxycycline treatment
• however, the absence of mature goblet cells is reversed by doxycycline-withdrawal and administration of dipenzazepine increased goblet cell numbers
|
|
• increased proliferation of epithelium cells in the crypt regions, villus regions and at the tip of the villi of undifferentiated progenitor cells in doxycycline-treated mice
• dipenzazepine administration decreases cell proliferation in the intestine of mice treated with doxycycline
• however, proliferation of undifferentiated cells is reversed by doxycycline-withdrawal
|
|
• in the epidermis of doxycycline-treated mice
|
|
• absent in the small intestine 5 days after doxycycline treatment
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lineage skewing is seen following prolonged doxycycline exposure (30 days)
|
|
• decrease in the proportion of B cell population (B220+)
|
|
• increase in the proportion of myelomonocytic (Cd11b+/Gr1+) and erythroid (CD71+/Ter119+) cells
|
|
• increase in nuclear size in sorted Lineage-/c-Kit+ progenitor cells not associated with an increase of genomic material or instability
|
|
• decrease in the number of GFP+ cells in the long-term (CD150+) and short-term (CD150-/CD48-) subsets
|
|
• decrease in the proportion of B cell population (B220+)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lineage skewing is seen following prolonged doxycycline exposure (30 days)
|
|
• in the splenic parenchyma
|
|
• decrease in the Ter119+ cell population
|
|
• decrease in the proportion of B cell population (B220+)
|
|
• increase in the proportion of myelomonocytic (Cd11b+/Gr1+) and erythroid (CD71+/Ter119+) cells
• increased amount of early erythroid (CD71+/Ter119+) cells in the spleen
|
|
• increase in nuclear size in sorted Lineage-/c-Kit+ progenitor cells not associated with an increase of genomic material or instability
|
|
• in the spleen
|
|
• decrease in the proportion of B cell population (B220+)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Col1a1tm1(tetO-Tcfap2c)Hsc/Col1a1+ Gt(ROSA)26Sortm1(rtTA*M2)Jae/Gt(ROSA)26Sor+ mice show increased proliferation and induced hepatic steatosis
|
• within 6 to 7 days of doxycycline treatment
|
|
• after doxycycline treatment, mice exhibit increased serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, lipase, amylase, lactate dehydrogenase levels compared with control mice
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment, hepatocytes exhibit abnormally bright mitochondria and increased mitophagy compared to in cells from control mice
|
|
• after doxycycline treatment, hepatocytes exhibit abnormally bright mitochondria
|
|
• after doxycycline treatment, mice exhibit microvesicular steatosis unlike control mice
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment, the proliferative zone is expanded to cover crypt and villus compared to in control mice
|
|
• after doxycycline treatment, the number of terminally differentiated intestinal cells (absorptive enterocytes, goblet cells, Paneth, cells and enteroendocrine cells) is reduced compared to in control mice
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment, the ratio of crypt length to villus length in the duodenum, jejunum, and ileum is increased compared to in control mice
|
|
• after doxycycline treatment, mice exhibit pancreatic injury unlike control mice
|
|
• after doxycycline treatment
|
| N |
• doxycycline-treated mice do not exhibit induction of inflammatory processes
|
|
• after doxycycline treatment, hepatocytes exhibit abnormally bright mitochondria
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment, the proliferative zone is expanded to cover crypt and villus compared to in control mice
|
|
• after doxycycline treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lineage skewing is seen following prolonged doxycycline exposure (30 days)
|
|
• in the splenic parenchyma
|
|
• decrease in the Ter119+ cell population
|
|
• hypercellular bone marrow with erythroid and megakaryocytic hypoplasia and marked myeloid hyperplasia
|
|
• in the GFP+ cells in the bone marrow
|
|
• in peripheral blood of aged mice
|
|
• decrease in the proportion of B cell population (B220+)
|
|
• increase in the proportion of myelomonocytic (Cd11b+/Gr1+) and erythroid (CD71+/Ter119+) cells
• increased amount of early erythroid (CD71+/Ter119+) cells in the spleen
|
|
• aged mice show marked expansion of myeloid elements (granulocytic > monocytic) in the peripheral blood
|
|
• increase in nuclear size in sorted Lineage-/c-Kit+ progenitor cells not associated with an increase of genomic material or instability
|
|
• decrease in the number of GFP+ cells in the long-term (CD150+) and short-term (CD150-/CD48-) subsets
• compensated for with an increase in the CD150+/CD48+ multipotent progenitor subset
|
|
• in the spleen
|
|
• in aged mice
|
|
• aged mice show marked expansion of myeloid elements (granulocytic > monocytic) in the peripheral blood
|
|
• in peripheral blood of aged mice
|
|
• decrease in the proportion of B cell population (B220+)
|
|
• in aged mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| myeloproliferative neoplasm | DOID:2226 | J:229031 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 die within 14 days due to rapid and lethal myeloproliferative disease
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 exhibit increased liver size compared with similarly treated mice reconstituted with wild-type bone marrow
|
|
• modestly in doxycycline-treated wild-type mice reconstituted with bone marrow
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 die within 14 days due to rapid and lethal myeloproliferative disease
|
|
• wild-type mice reconstituted with bone marrow and treated with doxycycline exhibit a decrease in myeloid progenitor and myeloid erythrocroid progenitor cells compared with mice reconstituted with wild-type bone marrow
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• at 6 weeks, but not 16 weeks, in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• at 6 and 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• at 6 and 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• at 6 weeks, but not 16 weeks, in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• doxycycline-treated mice exhibit an expansion of hematopoietic stem cells (HSCs) due to preferential expansion of short term HSC compared with wild-type mice
• wild-type mice reconstituted with bone marrow and treated with doxycycline exhibit an increase in HSCs, hematopoietic progenitor cells, and long term HSCs compared with mice reconstituted with wild-type bone marrow
|
|
• at 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• at 6 and 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• modestly in doxycycline-treated wild-type mice reconstituted with bone marrow
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 exhibit an increase in the number of leukemic blasts and infiltration with immature myeloid cells compared with similarly treated wild-type mice reconstituted with wild-type bone marrow
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 exhibit increased liver size compared with similarly treated mice reconstituted with wild-type bone marrow
|
|
• modestly in doxycycline-treated wild-type mice reconstituted with bone marrow
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 die within 14 days due to rapid and lethal myeloproliferative disease
|
|
• at 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• at 6 and 16 weeks in wild-type mice reconstituted with bone marrow and treated with doxycyline
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• modestly in doxycycline-treated wild-type mice reconstituted with bone marrow
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1 exhibit increased liver size compared with similarly treated mice reconstituted with wild-type bone marrow
|
|
• modestly in doxycycline-treated wild-type mice reconstituted with bone marrow
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
• in wild-type mice reconstituted with bone marrow, treated with doxycyline, and transduced with BCR-ABL1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice develop more macro- and microadenomas in the small intestinal and, to a lesser extent colon, compared with Apcmin heterozygotes
|
|
• doxycycline-treated mice develop more macro- and microadenomas in the small intestinal and, to a lesser extent colon, compared with Apcmin heterozygotes
• doxycycline-treated mice exhibit increased size of microadenomas compared with Apcmin heterozygotes
|
|
• doxycycline-treated mice exhibit loss of imprinting and increased expression of Igf2 compared with control mice
• doxycycline-treated mice exhibit biallelic methylation of H19 differentially methylated region in tumors and normal colon epithelial cells compared with control mice
• doxycycline-treated mice exhibit hypermethylation of Sfrp2, Sfrp4 and Sfrp5 in tumors and normal colon epithelial cells unlike control mice
• however, mice exhibit normal methylation of of Snrpn differentially methylated region in tumors and normal colon epithelial cells, and global DNA methylation
|
|
• doxycycline-treated mice develop more macro- and microadenomas in the small intestinal and, to a lesser extent colon, compared with Apcmin heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal villus compartment
|
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• docycycline-treated mice exhibit apoptosis all along the enlarged crypt axis instead of being restricted to the bottom of the crypt as in control mice
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• upon withdrawal of doxycycline
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• increased in the crypt compartment of doxycycline-treated mice
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• doxycycline-treated mice exhibit partially altered intestinal differentiation compared with control mice
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• enlarged crypts in doxycycline-treated mice
• however, withdrawal of doxycycline leads to a rapid regression of the crypt compartment
|
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• in docycycline-treated mice
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• enlarged crypts in doxycycline-treated mice
• however, withdrawal of doxycycline leads to a rapid regression of the crypt compartment
|
|
• docycycline-treated mice exhibit apoptosis all along the enlarged crypt axis instead of being restricted to the bottom of the crypt as in control mice
|
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• upon withdrawal of doxycycline
|
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• increased in the crypt compartment of doxycycline-treated mice
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following doxycycline treatment mice gain less weight when fed a high fat diet compared to wild-type mice
|
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• following doxycycline treatment mice gain less weight when fed a high fat diet compared to wild-type mice
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• following doxycycline treatment average fasting glucose is less than 50 mg/dL
|
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• following doxycycline treatment on a normal or high fat diet
|
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• following doxycycline treatment
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following doxycycline treatment
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• following doxycycline treatment
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• in the fed state following doxycycline treatment
|
|
• during a glucose tolerance test in doxycycline treated mice
• however, no difference in insulin sensitivity is detected following doxycycline treatment
|
|
• following doxycycline treatment on a normal or high fat diet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following doxycycline treatment responses in a glucose tolerance test are similar to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• half of mice treated with doxycycline between 5 and 10 weeks of age die prematurely
|
|
• in doxycycline-treated mice
|
|
• doxycycline-treated mice exhibit cell cycle arrest in the liver, spleen, and intestine unlike control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice treated with doxycycline between 5 and 10 weeks of age die prematurely
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice treated with doxycycline between 5 and 10 weeks of age die prematurely
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in doxycycline-treated mice
|
|
• at 6 to 7 months of age in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice
|
|
• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable and healthy in the absence of tamoxifen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal salivary gland morphology
|
|
• salivary glands exhibit an increase in luminescence compared to in Gt(ROSA)26Sortm1.2Tiw heterozygotes indicating increased endoplasmic reticulum (ER) stress
• however, mice exhibit normal production and secretion of salivary amylase
|
|
• mouse embryonic fibroblasts exhibit an increase in endoplasmic reticulum (ER) stress induced by amylase over-production compared with similarly treated wild-type cells
• however, over-expression of Dnajc10 mitigates ER stress induced by amylase over-production
|
|
• salivary glands exhibit an increase in luminescence compared to in Gt(ROSA)26Sortm1.2Tiw heterozygotes indicating increased endoplasmic reticulum (ER) stress
• however, mice exhibit normal production and secretion of salivary amylase
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• phenotype is stated to be identical to that of Wnt9btm1.1Amc homozygotes; however only limited data is presented
|
|
• no pretubular aggregates are apparent
|
|
• development is arrested
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a reduction in amyloid plaques compared with Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte mice
|
|
• mice exhibit a reduction in amyloid plaques compared with Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when mice are fed a high-fat diet compared with controls
|
|
• when mice are fed a high-fat diet compared with controls
|
|
• 3-fold from isolated islets treated with glucose
• however, response to arginine or KCl is normal and first-phase secretion is normal
|
|
• 3-fold from isolated islets treated with glucose
• however, response to arginine or KCl is normal and first-phase secretion is normal
|
|
• when mice are fed a high-fat diet despite comparable food intake
|
|
• mice fed a high-fat diet exhibit reduced fasting glucose levels compared with control mice fed the same diet
|
|
• mice fed a high-fat diet exhibit reduced insulin levels compared with control mice fed the same diet
|
|
• when mice are fed a high-fat diet compared with controls
|
|
• when mice are fed a high-fat diet compared with controls
|
|
• when mice are fed a high-fat diet despite comparable food intake
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 5 weeks of age, the only mouse born shows no apparent developmental defects and is morphologically indistinguishable from wild-type littermates; Western blot analysis confirmed expression of the full-length human DIS3L protein product, indicating successful rescue of the embryonic lethal phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when dox treatment was started at E15.5, all 3 double mutants died at birth
|
|
• in dox treated mice, distal epithelium remains columnar failing to undergo the columnar to squamous transition
|
|
• when dox treatment is started at E9.5 or E15.5, terminal differentiation of airway cells is inhibited and all differentiated cells are Sox9-negative
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show reduced concentrations of human amyloid beta40 and amyloid beta42 peptides in cortical and hippocampal extracts
• however, basal concentrations of brain interstitial fluid amyloid beta40 are unchanged in the brain parenchyma of adults compared to single Tg(APPV717F)109Ili mice
• concentrations of the soluble human APP alpha and APP beta are not affected
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 01/20/2026 MGI 6.24 |
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