Analysis Tools
normal phenotype
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• homozygotes are viable and fertile with no gross abnormalities
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Allele Symbol Allele Name Allele ID |
Gt(ROSA)26Sortm1(DTA)Jpmb targeted mutation 1, Juan Pedro Martinez-Barbera MGI:3610389 |
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| Summary |
18 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes are viable and fertile with no gross abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lethality occurs around E9.5
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• at the 12-14 somite stage no heart is present
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• at E9.5 embryos are very small and some are partially resorbed
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• at E9.5 embryos are very small and some are partially resorbed
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5 and E10.5, the cranial neural tube is open dorsally
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• at E9.5 and E10.5, the isthmus (the constriction of the neural tube at the midbrain hindbrain boundary) is absent
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• at E9.5 and E10.5 the brain rostral to the otic vesicle is significantly smaller
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• at E9.5 and E10.5, the cranial neural tube is open dorsally
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• clara cell numbers recover after tamoxifen and/or naphthalene lung injury regardless of presence or absence of pulmonary neuroendocrine cells
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• 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
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| ♀ | 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
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• 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
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• 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)
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| 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
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• mutants have reduced numbers of TRPV2-containing sensory neurons
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• 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
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• 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
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• mutants display complete loss of behavioral responses to injection of pruritogenic compounds
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• with tamoxifen treatment at E12.5, presence of a single copy of Spry1 only marginally improves the hypoplasia observed at E19.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 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
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• 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
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• when tamoxifen is administered at E9.5, about half the fetuses display renal agenesis at E18.5
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| ♀ | 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
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• cardiovascular developmental abnormalities result in in utero death
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• yolk sacs of mutant embryos have almost no vasculature compared to controls
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• observed in E10.5 embryos
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| N |
• in mutants, ventricular myocardium and endothelial layer are intact
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• vessels are weakened and hemorrhagic in embryos
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• dorsal aorta is fragmented and contains only a few smooth muscle cells
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• yolk sacs of mutant embryos have almost no vasculature compared to controls
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• atrioventricular (AV) cushion region is largely absent in mutants
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• cushion hypoplasia is observed at E10
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• E10.5 embryos have smaller hearts relative to controls
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• E10.5 embryos are hemorrhagic
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• observed in E10.5 embryos
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• approximately 20% of mice die suddenly with no ante-mortem indication of illness within 60 days after high dose tamoxifen treatment
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• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
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• tamoxifen induced ablation of sinoatrial node cells is accompanied by a destructive fibrosis of nodal tissue
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• 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
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• following 5 days of high or low dose tamoxifen treatment heart rate falls by about 40 - 50% or 12%, respectively
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• variety of cardiac rhythm disturbances; including sino-atrial arrhythmia, sino-atrial pause and to a minor extent supraventricular or ventricular tachycardia, following tamoxifen treatment
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• complete heart block some weeks after tamoxifen treatment
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• 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
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• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| sick sinus syndrome | DOID:13884 |
OMIM:163800 OMIM:608567 |
J:186021 | |
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| ♀ | 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
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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 |
| N |
• embryos retain their heads and appear normal at E10.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• significantly disturbed after 3 days of tamoxifen treatment (which results in loss of more than 50% of insterstitial cells of Cajal (ICCs)
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• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity
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• 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)
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• tamoxifen-treated mice have delayed gastric emptying
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• in tamoxifen treated mice, excitatory enteric neurotransmission is blocked as result of ICC depletion
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• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity
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| ♀ | 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
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• 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
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• 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
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• following tamoxifen treatment, mice develop variable retinal folds termed rossetting unlike wild-type mice
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• under scotopic conditions at 6 weeks and 6 months, tamoxifen-treated mice exhibit decreased a and b wave amplitudes compared with wild-type mice
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about 50% of mice die 52 weeks after tamoxifen injection
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• 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
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• 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
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• white matter lesions in tamoxifen injected mice show presence of macrophages containing myelin debris and unmyelinated axons, indicating ongoing demyelination
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• 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
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• thinner myelin in both tamoxifen treated and untreated mice (due to leakiness of the cre-expressing transgene)
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• axonal loss in the ventrolateral white matter of the cervical spinal cord (40%) and the optic nerve (55%) at 1 year after tamoxifen treatment
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• 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
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• mice show impaired motor skills starting around 40 weeks after tamoxifen injection
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• tamoxifen treated mice exhibit severe ataxia starting around 40 weeks after injection
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• mice show weight loss starting around 40 weeks after tamoxifen injection
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• 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
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• 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
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• 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
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• 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
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:234435 | |
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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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• treatment of mice with tamoxifen results in an expansion of Krt7-expressing cells from their ordered appearance at the squamocolumnar junction to more anterior regions of the proximal stomach; the migrating Krt7+ cells do not have squamous properties
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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 05/14/2024 MGI 6.23 |
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