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Allele Symbol Allele Name Allele ID |
Meox2tm1(cre)Sor targeted mutation 1, Philippe Soriano MGI:2176174 |
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| Summary |
76 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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryos are recovered at normal numbers at E12.5-E14.5; however, all embryos die between E15.5 and E17.5
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• at E15.5, embryos are smaller than control embryos
• however, embryos are grossly normal at E13.5
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• at E15.5, embryos display whole-body edema
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• starting at E13.5, hearts show morphological defects that resemble congenital cardiac defects seen in Noonan syndrome patients
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• at E13.5, hearts exhibit myocardial hypertrabeculation
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• at E13.5, the compact layer thickness in the right and left heart ventricle is reduced by 62.5 and 45.5%, respectively
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• at E13.5, 4 of 6 hearts exhibit a thin myocardium
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• at E13.5, hearts exhibit downregulated non-canonical Wnt and BMP pathways and hyperactivated MEK/ERK signaling, indicating dysregulation of critical pathways involved in heart development
• however, no alterations in cell proliferation or apoptosis are observed in the heart at E13.5
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• pulmonary valves are not remodeled properly
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• at E13.5, 4 of 6 hearts exhibit a DORV phenotype, where both the aorta and pulmonary trunk exit the right ventricle
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• at E13.5, all (6 of 6) hearts show ventricular septal defects (VSDs); the interventricular septum fails to fuse with the endocardial cushion, unlike in control hearts
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• at E13.5, 4 of 6 hearts exhibit pulmonary valve stenosis
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• at E15.5, hepatic necrosis is observed, esp. in the regions distal from blood flow
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• fetal livers are smaller at E15.5
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• fetal liver hematopoiesis is mildly perturbed at E13.5
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• at E13.5, fetal livers show a moderate expansion of Ter119- CD71mid/hi cells that are enriched with colony forming unit-erythroid (CFU-E) progenitors and early erythroblasts
• however, the % of terminally differentiating Ter119+ erythroid cells is similar to that of controls
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• at E13.5, embryos show a moderate expansion of hematopoietic stem and progenitor cells in the fetal liver
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• at E13.5, embryos show a moderate expansion of hematopoietic stem and progenitor cells in the fetal liver; both HSCs (defined as Lin- Mac1+ CD41- CD48- CD150+ Sca1+ cKit+) and LSK cells (hematopoietic stem and progenitor cells, defined as Lin- Sca1+ cKit+) are expanded
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• at E15.5, hepatic necrosis is observed, esp. in the regions distal from blood flow
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• at E13.5, hearts exhibit myocardial hypertrabeculation
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• at E13.5, the compact layer thickness in the right and left heart ventricle is reduced by 62.5 and 45.5%, respectively
|
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• at E13.5, 4 of 6 hearts exhibit a thin myocardium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die by P8-P10
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• progressive age related relative decrease in length and weight
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• slightly but significantly decreased at P7
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• neuron soma size is reduced in the cerebral cortex
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• cerebellar atrophy at P7
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• reduced cross section areas of the pancreatic acini at P7
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• at P7 as indicated by reduced pancreas elastase levels in the stool and reduced cross section areas of the pancreatic acini
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• decreased myocyte soma size
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• decreased soma size
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• reduced cross section areas of the pancreatic acini at P7
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• at P7 as indicated by reduced pancreas elastase levels in the stool and reduced cross section areas of the pancreatic acini
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die within 24 hours after birth
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• areas affected with rosette-like structures are rich in dilated blood vessels
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• moderate hemorrhage in the ventricles of the brain, detected as early as E12.5
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• dome-like shape of head
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• the apical-junctional complex in the neuroepithelium of E10.5 mutants is disrupted; pseudostratified neuroepithelium in the wild-type embryos is replaced by stratified neuroepithelium in the mutant
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• formation of neuroepithelial rosette-like structures similar to the neuroblastic rosettes in human primitive neuroectodermal tumors
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• areas affected with rosette-like structures are rich in dilated blood vessels
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• moderate hemorrhage in the ventricles of the brain, detected as early as E12.5
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• many neural progenitor cells fail to exit the cell cycle and differentiate, and instead, continue to proliferate and die by apoptosis
• neural progenitor cells exhibit a loss of cell polarity
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• many neural progenitor cells fail to differentiate, and instead continue to proliferate
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• the apical-junctional complex in the neuroepithelium of E10.5 mutants is disrupted; pseudostratified neuroepithelium in the wild-type embryos is replaced by stratified neuroepithelium in the mutant
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• formation of neuroepithelial rosette-like structures similar to the neuroblastic rosettes in human primitive neuroectodermal tumors
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• newborns develop severe hydrocephalus
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• ventricles become dilated by E15.5
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• lateral ventricles of newborns appear dilated due to accumulation of cerebrospinal fluid and increasing pressure
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• expansion of the striatum region of the brain at E12.5, where the neuroepithelial cell layer extends into the zones normally occupied by differentiating cells and forms aberrant rosette-like structures
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• ventricular surface of cerebral cortex is destroyed and the subventricular structures are severely damaged
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• overall increase in the neural progenitor cell domain and decrease in the differentiated neuronal cell domain
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• overall reduction of in the numbers of differentiated neurons in the striatum region
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• dome-like shape of head
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• many neural progenitor cells fail to exit the cell cycle and differentiate, and instead, continue to proliferate and die by apoptosis
• neural progenitor cells exhibit a loss of cell polarity
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• many neural progenitor cells fail to differentiate, and instead continue to proliferate
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• partial rescue of the null phenotype with some embryos displaying all defects seen in mice homozygous for Zfp568chato, some displaying only the extraembryonic defects, and some having a wild-type phenotype
• the degree of rescue is at least partially related to the degree of cre mediated recombination
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• live embryos are present at E10.5 but none survive to birth
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• myeloproliferative CML-like disease by 3-6 months of age
• massive infiltration of bone marrow and spleen with neutrophilic granulocytes
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• tibia length was reduced by 6 months
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• 70% reduction in numbers of osteoclasts
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• tibia length was reduced by 6 months
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• severe osteopenia by 4 weeks of age wihich progressed with age
• bones were thin and brittle by 7 days of age
• by 1 month, vertebral bone mass was decreased
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• cortical bone thickness severely reduced at 6 months
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• number of osteoblasts is reduced by 7 days
• osteoblast numbers reduced up to 90% by 6 months
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• defective osteoclast differentiation
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• 60% reduction in cortical bone formation at 1 month, 40% reduction at 3 months
• 70% reduction in trabecular bone formation at 1 month, 30% reduction at 3 months
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• bone resorption significantly reduced
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• bone strength was significantly reduced
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• defective osteoclast differentiation
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• 70% reduction in numbers of osteoclasts
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• defective osteoclast differentiation
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• 70% reduction in numbers of osteoclasts
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• defective osteoclast differentiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• deposition of mineralized extracellular matrix is strongly reduced
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• progressive loss of bone mass
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• reduced bone mass is seen in the lumbar vertebral bodies and long bones and vertebral trabecular thickness is reduced in 6 week and 3 month old mutants
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| N |
• transaortic constriction of the aorta (TAC) results in a comparable hypertrophic response as in controls
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| N |
• in a model of liver fibrosis, mice exhibit a normal response
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• deposition of mineralized extracellular matrix is strongly reduced
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• with conditional deletion in the epiblast, no homozygous embryos are detected 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 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lungs at E12.5 show increased branching compared to Kras; Meox2-cre, Spry2-wild-type lungs; bronchi number is increased, but is still less than age-matched wild-type
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos survive as late as E9.5 when death occurs due to severe vascular defects
|
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• numerous apoptotic cells are observed in the posterior bulge of allantois in mutant embryos at E8.5
|
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• at E9.5, 46% of mutant embryos show reversed axial rotation compared to no control embryos
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• at E8.5, poorly formed allantois with failure to fuse dorsally with the chorion is observed; there is a prominent dorsal bulge extruding dorsally. close to primitive streak
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• at E9.5, some mutant embryos display reversed position of the atrioventricular canal and outflow tract
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• in 23% of embryos at E9.5, there is a vertical heart tube with ambiguous looping direction
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• at E9.5, in some embryos canal is reversed with outflow tract
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• in 40% of mutant embryos, heart looping is reversed, whereas 37% show normal looping and remainder are ambiguous
|
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• numerous apoptotic cells are observed in the posterior bulge of allantois in mutant embryos at E8.5
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit neuraxis-wide apoptosis during development unlike in wild-type mice
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die around E8
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• at E7.5
|
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• at E7.5, yolk sacs are cone-shaped
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• at E7.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• although born alive death occurs around 21 days of age from aggressive neurodegenerative disease
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• after being born alive, pups show progressive growth retardation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit an aortic vascular ring
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• cardiac malformations
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• dextroposition (one of four)
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• mice exhibit axial and appendicular skeletal defects similar to those in Pcsk5vcc homozygotes
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• mice exhibit a presacral mass protruding ventrally from the caudal end of the spinal cord and vertebral column in mice lacking a tail
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• absent
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• in some mice
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• in some mice
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• in the left lung
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• mice exhibit a presacral mass protruding ventrally from the caudal end of the spinal cord and vertebral column in mice lacking a tail
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• absent
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• absent
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die around mid-gestation
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit no obvious morphological abnormalities
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal weight, weight gain and growth
|
| N |
• normal survival
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at weaning
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• no survival beyond ~84 days
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Aicardi-Goutieres syndrome | DOID:0050629 |
OMIM:225750 OMIM:610181 OMIM:610329 OMIM:610333 OMIM:612952 OMIM:615010 OMIM:615846 OMIM:PS225750 |
J:308678 | |
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• loss of imprinting of ubiquitously imprinted genes when the Kcnq1ot1 allele is inherited paternally
• no alteration of imprinting status when the Kcnq1ot1 allele is inherited maternally
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• at 4 weeks of age when the Kcnq1ot1 allele is inherited maternally
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryoes that express the cre knock-in allele during development die at birth from respiratory distress
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• E18.5 embryos are smaller than controls
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• E18.5 pups have shortened or absent tails
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• E18.5 pups have shortened or absent tails
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• the airways and alveoli of E18.5 embryos are collapsed
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• pups die at birth from apparent respiratory failure
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• 18.5 embryos have incomplete closure of the sternum
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• 18.5 embryos have an assymmetric fusion of the ribs to the sternum
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• 14 of 15 embryos have one to three additional ribs attached to the sternum
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• 10 of 15 embryos have 3 to 4 additional thoracic vertebrae, 8 lumbar vertebrae, and only three to nine sacral and caudal vertebrae
• none of the embryos have the normal complement of vertebraes
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• ossification is retarded namely in the mandibles, nasal bone, vertebrae and limbs
|
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• all E18.5 embryos lack at least one kidney with only 1/6th of the mice having a normal kidney
|
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• most E18.5 embryos have abdominal herniations
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• subepidermal hemorrhages occur on the head or along the spine amongst the smallest 18.5 embryos
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants display an open neural tube at E9.5
|
| N |
• in E8.5 cranial fold explants cultured for 48 hours, neural crest cell delamination and migration are observed, similar to control explants
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• double mutants display an open neural tube at E9.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die by E12.5
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• embryos are malformed by E10 with a high index of apoptosis
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• embryos are malformed by E10 with a high index of apoptosis
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• embryos are malformed by E10 with a high index of apoptosis
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|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• authors state that mice exhibit the same defects as observed in Pak4tm2.1Amin/Pak4tm2.2Amin Tg(Sox2-cre)1Amc mice
|
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• authors state that mice exhibit the same defects as observed in Pak4tm2.1Amin/Pak4tm2.2Amin Tg(Sox2-cre)1Amc mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than expected mice survive to birth but more than in Pkd1tm1Ggg homozygotes
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• mice that are born alive die shortly after birth
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• placental abnormalities observed in Pkd1tm1Ggg homozygotes are partially rescued
|
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• some mice exhibit fewer fetal vessels and more dilated vascular spaces in the placenta compared with wild-type mice
• on average, fetal vessel density in the placenta is decreased compared to in wild-type mice
|
| N |
• edematous mice exhibit normal heart morphology
|
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• some mice exhibit fewer fetal vessels and more dilated vascular spaces in the placenta compared with wild-type mice
• on average, fetal vessel density in the placenta is decreased compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• homozygous embryos die by E14.5
|
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• embryos are recovered at a lower frequency (15% vs expected 25%) at E13.5
|
| N |
• mutants show normal vascularization of the yolk sac and placental labyrinth
|
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• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
|
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• excess cushion tissue often leads to obstructed outflow tract
|
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• at E13.5, embryos frequently show double outlet right ventricle
|
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• atrioventricular valve malformations
|
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• all embryonic hearts have prominent septal defects
|
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• heart defects lead to heart failure and death in embryos by ~E14.5
|
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• embryos appear normal at E12.5, but rapidly develop peripheral hemorrhages by E13.5, consistent with heart failure
|
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• red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation
|
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• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
|
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• defects in lung branching are apparent by E11.5 compared to controls in vivo and in cultured lungs
• decrease in branching is associated with formation of large, fluid-filled sacs rather than normal terminal branches
|
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• at E12.5, mutant lungs exhibit large dilated bronchi whereas wild-type lungs show secondary and tertiary bronchi
• at E14.5, mutants lungs display dilated bronchi and only a few terminal bronchi
|
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• at E14.5, mutants lungs display only a few terminal bronchioles
|
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• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5
|
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• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5
|
|
• at E12.5 fetal livers show large areas of apoptosis
|
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• at E12.5, fetal livers appear hypocellular
|
|
• embryos appear normal at E12.5, but rapidly develop edema by E13.5, consistent with heart failure
|
|
• embryos appear normal at E12.5, but rapidly develop pallor by E13.5, consistent with heart failure
|
|
• at E12.5 fetal livers show large areas of apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike homozygous null mice, mice with conditional deletion in embryonic tissues that retain expression in the extraembryonic visceral endoderm and in the placenta survive past birth
|
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• at 18 - 22 days of age
|
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• hypochromic at P10
• reduced in both mature erythrocytes and reticulocytes at 18 - 22 days of age
|
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• at 18 - 22 days of age
|
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• at P10
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• at P10
|
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• at P10 and at P18 - P22
|
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• significant iron accumulation in splenic macrophages at P12
• at P18 - P22 spleen iron are increased 4.4-fold increase compared to controls
|
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• apparent within a few days of birth
• difference from controls becomes more prominent with age
|
|
• significant iron accumulation in duodenal enterocytes at P12
|
|
• significant iron accumulation in splenic macrophages at P12
• at P18 - P22 spleen iron are increased 4.4-fold increase compared to controls
|
|
• significant iron accumulation in the Kupffer cells and hepatocytes at P12
• at P18 - P22 iron levels in the liver are reduced by 1.7-fold compared to controls
|
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• significant iron accumulation in duodenal enterocytes at P12
|
|
• significant iron accumulation in splenic macrophages at P12
• at P18 - P22 spleen iron are increased 4.4-fold increase compared to controls
|
|
• significant iron accumulation in the Kupffer cells and hepatocytes at P12
• at P18 - P22 iron levels in the liver are reduced by 1.7-fold compared to controls
|
|
• apparent within a few days of birth
• difference from controls becomes more prominent with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike germline null mice, no placental abnormalities are seen
|
| N |
• unlike germline null mice, no liver hypoplasia is seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• onset of mammary tumors with a median onset of 137 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 137 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 137 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• delayed onset of mammary tumors with a median onset of 174 days, a significant delay of 37 days from control group
• once tumors appeared, the rate of tumor growth was not detectably altered
|
|
• delayed onset of mammary tumors with a median onset of 174 days, a significant delay of 37 days from control group
• once tumors appeared, the rate of tumor growth was not detectably altered
|
 |
• the epithelial hyperplasia of mutant mice filled less of the mammary fat pad than control
|
|
• delayed onset of mammary tumors with a median onset of 174 days, a significant delay of 37 days from control group
• once tumors appeared, the rate of tumor growth was not detectably altered
|
|
|
• the epithelial hyperplasia of mutant mice filled less of the mammary fat pad than control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no embryos recovered past E3.5
|
|
• blastocysts are unable to form outgrowths upon in vitro culture
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• less than Mendelian ratios of mice are recovered at 2 weeks after birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• less than Mendelian ratios of mice are recovered at 2 weeks after birth
|
|
|
• 100% of mice have polydactyly restricted to digits I or II of either the hindlimbs or forelimbs
• Background Sensitivity: on the 129S4/SvJaeSor background defects are restricted to only the last phalange
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit reduced uptake of intrinsic factor vitamin B12 complex and apoA-I by proximal tubule cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• less than Mendelian ratios of mice are recovered at 2 weeks after birth
• Background Sensitivity: postnatal lethality is more severe in a 129S4/SvJaeSor background than in a mixed 129S4/SvJaeSor C57BL/6 background
|
|
|
| ♀ | 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 |
|
• all mice show cardiac defects
|
|
• ventricular septal defect
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly lower than expected ratio of live embryos were obtained at E13.5 and E17.5, presumed to indicate embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• lack spermatogonia
|
|
• lack of primordial germ cells by E14.5 (early germ cell marker Mvh absent)
|
|
• primordial germ cells migrate to genital ridge but fail to proliferate normally between 11.5 and 14.5 dpc
|
|
|
• significantly smaller testes at 6 wks of age
|
|
|
• no sign of spermatogenesis detected at 2 wks of age, due to spermatogonia cell depletion
|
|
|
• absence of spermatids in seminiferous tubules
|
|
|
• absence of spermatocytes in seminiferous tubules
|
|
• both sexes are sterile
|
|
|
• absence of spermatids in seminiferous tubules
|
|
|
• absence of spermatocytes in seminiferous tubules
|
|
|
• lack spermatogonia
|
|
• lack of primordial germ cells by E14.5 (early germ cell marker Mvh absent)
|
|
• abnormal centrosome number (>2) in some mutant PGCs at 13.5 dpc
|
|
• abnormal centrosome number (>2) in some mutant PGCs at 13.5 dpc
|
|
• abnormal metaphase configuration of mutant PGCs at 13.5 dpc
• precocious sister chromatid separation and arrest of PGCs in mitosis due to spindle checkpoint activation
|
|
• significantly higher mitotic indices in mutant PGCs than controls at 12.5, 13.5, and 14.5 dpc
|
|
• primordial germ cells migrate to genital ridge but fail to proliferate normally between 11.5 and 14.5 dpc
|
|
• higher levels of activated caspase-3, p53, and Bax in extracts of 13.5 dpc mutant genital ridges than in controls, suggesting p53-related apoptosis of mutant PGCs
|
|
|
• significantly smaller testes at 6 wks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants have slightly increased thrombin-antithrombin (TAT) complex levels
|
|
• 2-month old mice show decreased platelet counts compared to wild-type; differences increase and become significant with age
|
|
• circulating levels are higher in 2 month old mutants
• however, after thrombin infusion, circulating APC (activated protein C) levels are only 5.2% that of wild-type controls
|
|
• fibrinogen levels are decreased relative to wild-type; differences increase and become significant with age
|
|
• circulating levels are higher in 2 month old mutants
• however, after thrombin infusion, circulating APC (activated protein C) levels are only 5.2% that of wild-type controls
|
|
• fibrinogen levels are decreased relative to wild-type; differences increase and become significant with age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no Procr-null, Meox2 heterozygous mice are obtained
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die shortly after birth, however a few mice live to adulthood
|
|
• mice exhibit albuminuria to the same extent as conditional homozygous Cubn mice
|
|
• mice exhibit albuminuria to the same extent as conditional homozygous Cubn mice
|
|
• renal morphology is similar to that in single homozygous Lrp2 mice
|
|
• absence of uptake of apoA-I by proximal tubule cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only 19% of the expected 25% of mice are observed indicating some lethality
|
|
• selective daily albumin excretion is increased about 6-fold
|
|
• plasma levels of vitamin B12 are severely decreased due to absence of uptake of intrinsic factor vitamin B12 complex in the ileum
|
|
• selective daily albumin excretion is increased about 6-fold
|
|
• mice exhibit a decrease in uptake of albumin and no uptake of intrinsic factor vitamin B12 complex by proximal tubule cells
• however, urinary tubular uptake or excretion of vitamin D-binding protein is not affected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• viable, with about 10% of cells still expressing DAB2 protein
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• less than Mendelian ratios of mice are recovered at 2 weeks after birth
|
|
|
• 100% of mice have polydactyly restricted to digits I or II of either the hindlimbs or forelimbs
|
|
|
• the perichondrium around forming digits is poorly organized
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Vitamin D binding protein and retinol binding protein found in the urine
|
|
• Vitamin D binding protein and retinol binding protein found in the urine
|
|
• reduced numbers of coated pits and endocytic vescicles near the apical membrane of the proximal tubules
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• less than Mendelian ratios of mice are recovered at 2 weeks after birth
• Background Sensitivity: postnatal lethality is more severe in a 129S4/SvJaeSor background than in a mixed 129S4/SvJaeSor C57BL/6 background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• loss of paternal repeats does not affect expression of Rasgrf1 in neonatal brain
• loss of paternal repeats at E5.5 in the epiblast does not result in changes to methylation state of the paternal allele, in contrast with deletion earlier in development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• usually by P14
|
|
• during the second week
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• usually by P14
|
|
• during the second week
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Tg(CAG-lacZ,-FUS,-EGFP)629Gyu/0 Meox2tm1(cre)Sor/Meox2+ mice display hindlimb curl
|
• nearly 100% of mice die before P30
|
|
• body weights are different from controls starting at P4
|
|
• seen by P14
|
|
• seen at P14
|
|
• seen by P14
|
|
• mice develop gait abnormalities at P10
|
|
• end-stage mutants exhibit scattered and grouped atrophic muscle fibers and presence of pyknotic myofibers indicating muscle atrophy
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• mice, however do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
|
• mice that die by P30 exhibit activation of astrocytes in the brain and spinal cord
|
|
• end-stage mutants show abnormalities and degeneration of the neuromuscular junctions
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• mice, however do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• mice, however do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 6 | DOID:0060198 |
OMIM:608030 |
J:216672 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Tg(CAG-lacZ,-FUS*R521G,-EGFP)682Gyu/0 Meox2tm1(cre)Sor/Meox2+ mice display hindlimb curl
|
• about 50% of mice die before P30
|
|
• mice that survive past P30 exhibit reduced body mass
|
|
• mice that survive past P30 display a subtle motor impairment
|
|
• mice exhibit reduced righting ability, however to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice
|
|
• mice exhibit hindlimb clasping, but to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice
|
|
• on the rotarod, mice that escape early lethality show normal performance on day 1 of testing, however show impaired motor function on day 2 of testing
|
|
• mice exhibit reduced grip strength, however to a lesser extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice
|
|
• mice develop gait abnormalities that are less severe than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice
• gait analysis of mice that escape early lethality shows that the braking phase is greater in the forelimbs and the swing phase is reduced in the hindlimbs
• in the ladder-walking test, the forelimbs of mice that escape early lethality have more errors in stepping with few deficits in the hindlimbs
|
|
• mice that escape early lethality show less activity over a 9-day period on voluntary running wheels
• however, food intake is not altered
|
|
• interaction with juvenile mice is reduced at 4 months of age
• when introduced to intruder adult mice, mutants do not show any deficits before 8 months of age, at which time they show reduced chasing behavior
|
|
• end-stage mutants exhibit scattered and grouped atrophic muscle fibers, although to a lower extent than in conditional Tg(CAG-lacZ,-FUS,-EGFP)629Gyu mice
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord
• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
|
• mice that die by P30 exhibit activation of astrocytes in the brain and spinal cord
|
|
• dendritic intersections and cumulative area of dendrites are reduced in spinal motor neurons at P18 and these deficits are significant and persistent at P60
• fewer intersections and reduced cumulative area in the apical and basal dendrites in neurons of sensorimotor cortex layers IV-V at P18 and P60
|
|
• decrease in the number and density of mature spines
|
|
• end-stage mutants show abnormalities and degeneration of neuromuscular junctions
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord
• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
|
• mice that die by P30 exhibit activation of microglia in the brain and spinal cord
• however, mice that escape early lethality do not exhibit microglial and astrocyte activation in the brain and spinal cord
• mice also do not exhibit degeneration of axons in the dorsal corticospinal tract or lateral columns, or in the dorsal or ventral roots, indicating that descending motor axons are not altered, show no motor neuron loss in the cervical spinal cord, and no FUS protein aggregates in the brain or spinal cords
|
| N |
• mice exhibit normal olfaction and cognitive function
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 6 | DOID:0060198 |
OMIM:608030 |
J:216672 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• resistance to radiation induced DNA damage-induced apoptosis in neural tissues
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice are present at weaning
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die before 2 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
• onset of mammary tumors with a median onset of 132 days
• this mutant was used as control for Ets2tm3Rgo/Ets2tm3.1Rgo Meox2tm1(cre)Sor /? Tg(MMTV-PyVT*Y315F,Y322F)Db-1Mul/? mice to test the effect of Ets2 deficiency on mammary tumrigenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• development was variable
|
|
• fail to rotate their proximal distal axis
|
|
• variable amounts of anterior truncation at E6.5
• in severe cases an elongate morphology at E6.5
• profound anterior truncations by E8.5
|
|
• embryos occasionally protrude outside the yolk sac at E6.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutant mice survive through adulthood with no obvious defects
• both males and females are fully fertile and healthy to at least one year
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice surviving beyond P1 cannot easily regain posture when placed on their backs
|
|
• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
|
|
• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
|
|
• severe defect in postnatal cerebellar growth
|
|
• after birth, about one third of mutant mice die on postnatal day 1
|
|
• mutant mice that survive the neonatal period die by P17
• mutant pups are born at appropriate Mendelian ratio
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after birth, about one third of mutant mice die on postnatal day 1
|
|
• mutant pups are born at appropriate Mendelian ratio
• mutant mice that survive the neonatal period die by P17
|
|
• mice surviving beyond P1 cannot easily regain posture when placed on their backs
|
|
• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
|
|
• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
|
|
|
| ♀ | 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 |
|
• 24% of pups die at birth
|
|
• in severely affected newborns, the stomach is ruptured
|
|
• the stomach epithelium is very thin
|
|
• the muscular layer of the stomach is almost completely absent
|
|
• the muscular layer of the stomach is almost completely absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die between E11.5 and E15.5
|
|
• seen at E11.5 in some embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 21 days of thoracic aortic constriction (TAC), mutant hearts display only a 27.7% increase in heart weight/tibia length, compared to 59% in wild-type hearts
• mutant hearts undergo less cardiac remodeling than wild-type in response to TAC
• mutants do not display fibrosis as result of pressure overload hypertrophy while extensive fibrosis is observed in wild-type
|
|
• after pressure overload, mutant cardiomyocytes exhibit a considerably smaller increase in cross-sectional area composed to wild-type cardiomyocytes
|
|
• 21 days after TAC, mutant hearts show a smaller increase in heart weight/tibia length ratio versus wild-type
• after TAC, LV end-systolic diameter of mutant hearts is only marginally increased compared to wild-type hearts after TAC
|
|
• mutant hearts display a high level of resistance to reduction in heart muscle contractility after 21 days of TAC, whereas wild-type hearts show pronounced reduction in contractility
|
|
• after pressure overload, mutant cardiomyocytes exhibit a considerably smaller increase in cross-sectional area composed to wild-type cardiomyocytes
|
|
• mutant hearts display a high level of resistance to reduction in heart muscle contractility after 21 days of TAC, whereas wild-type hearts show pronounced reduction in contractility
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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 04/23/2024 MGI 6.23 |
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