Analysis Tools|
Allele Symbol Allele Name Allele ID |
Numbltm1Wmz targeted mutation 1, Weimin Zhong MGI:2429686 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable, fertile and exhibit no obvious phenotypes
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• mutant females showed decreased fertility
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• animals that were small tended to die between P5 and P21
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• mutants that survived to adulthood appeared jittery
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• mutants that survived to adulthood appeared to have normal life span but were solitary
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• mutants that survived to adulthood exhibited sporadic seizures
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• most mutant mice were slightly smaller than controls but were within the normal range of sizes and survived to adulthood
• occasionally, they reached only about one-third the size of their littermates
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• mutants that survived to adulthood exhibited sporadic seizures
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• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons
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• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region
• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization
• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex
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• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating
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• rough ventricular surfaces in mutant brains are suggestive of the shedding of brain tissues into the ventricle; shed tissues were occasionally found in the lateral ventricles
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• extensive ventricular enlargement
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• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating
• at E12.5, the forebrain exhibited undulating, folding, and invaginating with clumps of cells peeling into the lateral ventricle from the apical surface of the cortical ventricular zone
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• marginal zone absent and displayed no discernible laminar structures
• contained numerous cell clusters
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• shed tissues were occasionally found in the lateral ventricles
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• no identifiable corpus callosum in the caudodorsal region while corpus callosum in the rostral region was relatively normal
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• small thalamus
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• overgrown caudodorsal neocortex and thinning of the lateral cortex
• in extreme cases, the caudodorsal region was nearly missing, with just a thin layer of the cortex remaining with extreme ventricular enlargement
• the volume of the mutant cortex was increased
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• reduction in the number of mature neurons later in the double mutant animal was revealed by reduced expression of neuronal markers
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• multidendritic neurons, normally located in layer I, were distributed all over the mutant cortex
• Cajal-Retzius cells were displaced from the normal location in the outer layer of the neocortex to the ectopic sites across the cortex
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• 25% of the mutants displayed hypersensitivity to sound stimuli
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• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating
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• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons
|
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• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region
• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization
• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embyros die around E12.5
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• embryos are 80%-90% the size of wild-type littermates
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• thinned neural tube from the most rostral telencephalon to caudal spinal cord, including optic discs
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• frequent buckling of the surface
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• the neuroepithelium is only one-quarter to one-half the thickness of that in control littermates
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• severe neural progenitor cell loss
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• embryos are 80%-90% the size of wild-type littermates
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• thinned neural tube from the most rostral telencephalon to caudal spinal cord, including optic discs
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• frequent buckling of the surface
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• the neuroepithelium is only one-quarter to one-half the thickness of that in control littermates
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by P14 with tamoxifen induction at P0, pups show growth retardation
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• at P7, many striato-cortical junction cells are apoptotic
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• with tamoxifen induction at P0, by P14 induced animals show structural abnormalities along the lateral ventricle wall linings whereas uninduced animals do not
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• induced animals show consistent lateral ventricle enlargement by P7 compared to uninduced controls where slight enlargement is occasionally observed; by P14, enlargement is severe
• by 6 weeks of age, enlargement is significantly reduced
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• at P14, induced mutants display smaller olfactory bulbs with fewer interneurons, compared to uninduced controls with comparable brain size
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• at P14, the rostral migratory stream (RMS) of mutants contains fewer neuroblasts than controls
• in adult induced mutants (6 weeks old), there is recovery of neuroblast numbers in RMS into the olfactory bulb
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• at P14, the rostral migratory stream (RMS) of mutants contains fewer neuroblasts than controls
• in adult induced mutants (6 weeks old), there is recovery of neuroblast numbers in RMS into the olfactory bulb
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• at P7, induced animals show occasional gaps in the ependymal lining rather than a continuous lining; by P14, the gaps progress to ependymal detachment
• at P7, occasional defects in lateral wall integrity are seen compared to uninduced controls, but by P14, defects are severe with many areas having lost the ependyma and underlying subventricular zone (SVZ) niche
• at P7, induced mutants show a poorly formed ependyma with pseudocolumnar cells instead of a flat epithelial sheath; at P14, some ependymal cells detach and remaining cells form short, defective borders with separation between cells
• by 6 weeks of age, ventricular lining is composed of a multi-layered stratified epithelium instead of a single-cell layer seen in controls; epithelial barrier is composed of mixture of astrocytes and few ependymal cells, intermixed with scar tissue
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• at P7, many striato-cortical junction cells are apoptotic
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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 12/10/2024 MGI 6.24 |
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