Analysis Tools|
Allele Symbol Allele Name Allele ID |
Kif18agcd2 germ cell depletion, John Schimenti MGI:3050507 |
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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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• Background Sensitivity: at the 7th to 9th backcross generation on C57BL/6J, sterility is only 37%, much less than on the CAST/EiJ background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the percentage of homozygous embryos is less than normal, approximately 15% from a heterozygous intercross
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• Background Sensitivity: gonads are depleted of germ cells at birth and this has varying penetrance with greater severity on the CAST/EiJ background than the C57BL/6J background
• by embryonic day 11.5 there is a significant reduction in the average number of primordial germ cells and by embryonic day 11.5, after the proliferative phase of primordial germ cell development is normally complete, there are, on average, fewer than half the normal number of primordial germ cells
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• Background Sensitivity: at the 7th to 9th backcross generation on CAST/EiJ sterility is 90% penetrant
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• Background Sensitivity: gonads are depleted of germ cells at birth and this has varying penetrance with greater severity on the CAST/EiJ background than the C57BL/6J background
• by embryonic day 11.5 there is a significant reduction in the average number of primordial germ cells and by embryonic day 11.5, after the proliferative phase of primordial germ cell development is normally complete, there are, on average, fewer than half the normal number of primordial germ cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment
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• mutant fetal gonads exhibit cell cycle arrest and apoptosis, ultimately leading to germ cell depletion
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• primary MEFs derived from mutant E12.5-E13.5 embryos show reduced viability by trypan blue exclusion relative to wild-type MEFs
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• cell cycle analysis on E12.5 fetal gonads showed a significantly higher % of mutant germ (MVH+) cells in G2/M and a corresponding reduction in the % of germ cells in G1 relative to wild-type controls
• phosphorylated histone H3 and TUNEL labeling, both indicative of G2/M checkpoint activation, are significantly increased in mutant germ cells
• however, no significant differences in cell cycle distribution or histone H3 phosphorylation are detected in gonadal somatic (MVH-) cells
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• mutant MEFs show a 7-fold increase in the ratio of preanaphase mitotic cells with unaligned chromosomes; chromosomes are not aligned in live MEFs prior to anaphase
• mutant germ cells in the E12.5 fetal gonad exhibit similar chromosome alignment defects and undergo mitotic arrest
• however, mutant MEFs show no evidence of mitotic (G2 to M) arrest; progression from nuclear envelope breakdown to anaphase is comparable to wild-type
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• germ cell specific mitotic arrest due to kinetochore-microtubule attachment defects, as shown by persistent MAD2 localization to mutant kinetochores at metaphase in spermatogonia from pre-pubertal testes
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• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment
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• a significantly higher % of mutant fetal germ cells are TUNEL+, indicating increased apoptosis
• in contrast, mutant MEFs show no evidence of increased apoptosis
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• primary MEFs derived from mutant E12.5-E13.5 embryos grow slowly in culture relative to wild-type or heterozygous control MEFs
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• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment
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• mutant fetal gonads exhibit cell cycle arrest and apoptosis, ultimately leading to germ cell depletion
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• both male and female mutant mice are infertile
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• occurs in both sexes
(J:86161)
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| N |
• phenotype about 65% penetrant
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• at 20 to 22 weeks of age some homozygotes have normal appearing ovaries while others have tiny ovaries with few to no follicles and subfertile homozygotes have premature ovarian failure
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• Background Sensitivity: sterile female adults have a dramatic reduction in the number of growing follicles while the phenotype is less severe in fertile adult females and on this segregating background the phenotype varies considerably between individuals
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• subfertile homozygotes show premature ovarian failure with shortened reproductive life spans and small litters
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• occurs in both sexes
(J:86161)
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• spermatogenesis occurs in some but not all seminiferous tubules
(J:86161)
• Background Sensitivity: in the segregating background there is great variety in the percentage of seminiferous tubules that are depleted of germ cells, with the sterile homozygotes having a higher percentage than the fertile homozygotes
(J:111998)
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• sterility in both sexes
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• at 20 to 22 weeks of age some homozygotes have normal appearing ovaries while others have tiny ovaries with few to no follicles and subfertile homozygotes have premature ovarian failure
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• Background Sensitivity: sterile female adults have a dramatic reduction in the number of growing follicles while the phenotype is less severe in fertile adult females and on this segregating background the phenotype varies considerably between individuals
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• subfertile homozygotes show premature ovarian failure with shortened reproductive life spans and small litters
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• subfertile homozygotes show premature ovarian failure with shortened reproductive life spans and small litters
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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 10/09/2024 MGI 6.24 |
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