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Allele Symbol Allele Name Allele ID |
Chd7tm2c(EUCOMM)Wtsi targeted mutation 2c, Wellcome Trust Sanger Institute MGI:5749385 |
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| Summary |
12 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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• in the hippocampus at 12 weeks after tamoxifen treatment
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• at 8 months after tamoxifen injection there is a significant depletion of neuronal stem cells
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• at 12 weeks after tamoxifen treatment a significant decrease in the number of neuronal progenitors and immature neurons
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• increase in the number of progenitors and immature neurons 4 weeks after tamoxifen injection
• at 12 weeks after tamoxifen treatment radial neuronal stem cells numbers are increased almost 3-fold and the number of proliferating radial neuronal stem cells is increased over 2-fold
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• at 12 weeks and 8 months after tamoxifen treatment a significant decrease in the number of neuronal progenitors and immature neurons is seen
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• increase in the number of progenitors and immature neurons 4 weeks after tamoxifen injection
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• increase in proliferation in the subgranular zone 6-7 days after following tamoxifen injection
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• in the hippocampus at 12 weeks after tamoxifen treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:222062 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• a TUNEL assay showed that the rate of granulosa cell apoptosis in adult ovaries is significantly higher than in heterozygous control ovaries, esp. in the preantral and early antral follicles
• IHC showed that the expression of cleaved caspase-3 positive cells is significantly higher than in control females
• however, granulosa cell proliferation is normal, as determined by Ki-67 staining
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• the percentage of atretic follicles is significantly greater than in control females
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• H&E staining showed a significantly decreased number of ovarian follicles at all stages of folliculogenesis
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• at 8 weeks of age, ovaries are significantly smaller than in wild-type females
• however, body size is normal
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• however, body weight is normal
• at 8 weeks of age, ovary weights are significantly lower than in wild-type females
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• when mated with wild-type males for 6 months, females produce a significantly lower number of litters than wild-type or heterozygous controls
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• a TUNEL assay showed that the rate of granulosa cell apoptosis in adult ovaries is significantly higher than in heterozygous control ovaries, esp. in the preantral and early antral follicles
• IHC showed that the expression of cleaved caspase-3 positive cells is significantly higher than in control females
• however, granulosa cell proliferation is normal, as determined by Ki-67 staining
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• the percentage of atretic follicles is significantly greater than in control females
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• H&E staining showed a significantly decreased number of ovarian follicles at all stages of folliculogenesis
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• at 8 weeks of age, ovaries are significantly smaller than in wild-type females
• however, body size is normal
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• at 8 weeks of age, ovary weights are significantly lower than in wild-type females
• however, body weight is normal
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• a TUNEL assay showed that the rate of granulosa cell apoptosis in adult ovaries is significantly higher than in heterozygous control ovaries, esp. in the preantral and early antral follicles
• IHC showed that the expression of cleaved caspase-3 positive cells is significantly higher than in control females
• however, granulosa cell proliferation is normal, as determined by Ki-67 staining
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• rapid degeneration of inner hair cells at P10 and P14
• incidence is reduced compared to homozygous mice (5 of 24 mice)
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• degeneration of outer hair cells is slower than that of inner hair cells
• incidence is reduced compared to homozygous mice (5 of 24)
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• only 1 of 7 shows severe-profound hearing loss
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• rapid degeneration of inner hair cells at P10 and P14
• incidence is reduced compared to homozygous mice (5 of 24 mice)
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• degeneration of outer hair cells is slower than that of inner hair cells
• incidence is reduced compared to homozygous mice (5 of 24)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased granule cell precursor apoptosis in both the cerebellar vermis and hemispheres at P7, but is only statistically significant in the hemispheres
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• in vermis lobules I - VIII at early postnatal stages, but not in the hemispheres
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• rapid degeneration of inner hair cells at P10 and P14 in 6 of 8 and 15 of 16 mice, respectively
• however, inner hair cell development and morphology are similar to controls at P7
• by P21 most nuclei are missing, pyknotic, or fragmented
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• degeneration of outer hair cells is slower than that of inner hair cells
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• irregular
• delayed initiation of foliation in the vermis becomes evident at E17.5
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• hypoplasia in the hemispheres evident by P7
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• at P7 and P21 cells in the cerebellar vermis are organized in monolayers with small regions of slightly disorganized cells
• at P7, large patches of Purkinje cells are present in the cerebellar hemispheres
• distribution is irregular at E16.5 and mislocalized cells are evident in the cerebellar vermis and hemispheres by E18.5
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• in the cerebella at P21
• decrease is due to reduction in the number of cells in lobules I-VII
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• vermis folia IV-V and IX extend abnormally into the hemispheres
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• becomes evident at E18.5
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• at P21, with hypoplasia in lobules I - VIII, most strikingly in the central lobules
• becomes evident in the vermis at E18.5 and in the hemispheres by P7
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| N |
• no differences in vocalization, social investigation or olfactory discrimination
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• delay in acquiring the righting reflex
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• males but not females perform worse in a rotarod assay compared to sex-matched control littermates
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• delay in acquiring the righting reflex. negative geotaxis, ability to reach out toward an object
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• when explants of P6 cochlea are exposed to gentamicin for 5h more than half of the hair cells are lost, similar treatment of control cultures does not result in hair cell loss
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• increased granule cell precursor apoptosis in both the cerebellar vermis and hemispheres at P7, but is only statistically significant in the hemispheres
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• in vermis lobules I - VIII at early postnatal stages, but not in the hemispheres
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• rapid degeneration of inner hair cells at P10 and P14 in 6 of 8 and 15 of 16 mice, respectively
• however, inner hair cell development and morphology are similar to controls at P7
• by P21 most nuclei are missing, pyknotic, or fragmented
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• degeneration of outer hair cells is slower than that of inner hair cells
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• most (6 of 7) display severe-profound hearing loss across all frequencies at 4 and 8 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:314588 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• overexpression of Reln fully corrects the decrease in granule cell precursors seen in mutant mice without the Reln transgene at P1
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• overexpression of Reln rescues the decrease in lobule size for lobules VI-VII in female but not male mice
• no difference in Reln expression levels are seen between males and females
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• born at expected Mendelian ratios but only only 2 mice survived to P21
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• highly irregular foliation with apparently misdirected folia
• vermis folia IV-V and IX extend abnormally into the lateral hemispheres
• at P14 irregular foliation includes the expansion of vermis lobules IV-V and IX into the hemispheres
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• in surviving mice at P21
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• ectopic clusters of granule cells around clusters of Purkinje cells
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• at P0 the vermis hypoplasia is associated with failure to initiate the formation of most of the cardinal cerebellar fissures
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• at P0 the vermis hypoplasia is associated with failure to initiate the formation of most of the cardinal cerebellar fissures
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• at P0, hypoplasia is most clearly present in the cerebellar vermis
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• disproportionate reduction in cerebellar size at P21
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• pronounced hypoplasia of all cerebellar lobules in the vermis
• hypoplastic cerebellar hemispheres
• growth retardation is first evident at E16.5
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• survivors are smaller than control littermates
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in apoptosis in the external granule cell layer at postnatal stages
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• granule neuron progenitors show impaired cell cycle exit
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• cerebellar defects are more prominent in the anterior lobe
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• severe defects in folia formation at P0 and older, especially in the vermis
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• abnormal Purkinje cell distribution from P0 onwards, especially at the anterior lobe of the cerebellum
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• in the internal granule cell layer
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• at P0 and older but not at E15.5, especially in the vermis
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• increase in apoptosis in the external granule cell layer at postnatal stages
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• granule neuron progenitors show impaired cell cycle exit
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:243947 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• display largely perinatal lethality
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• conspicuous hypoplasia in surviving homozygous mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most show moderate hearing loss
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• rapid degeneration of neurons between P1 and P7, reducing numbers to 50% that of controls
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• rapid degeneration of spiral ganglion neurons between P1 and P7, reducing numbers to 50% that of controls
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:314588 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some show moderate hearing loss
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• slower degeneration of neurons between P1 and P21, reducing numbers to 50% that of controls by P21
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• slower degeneration of spiral ganglion neurons between P1 and P21, reducing numbers to 50% that of controls by P21
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen treatment at E16 does not result in postnatal hair cell degeneration unlike in mice where recombinase is active in the early embryonic period
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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 09/03/2024 MGI 6.24 |
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