mortality/aging
• homozygotes show partial embryonic lethality at ~E9.5-E14.5; from E12.5 on, the proportion of homozygotes is significantly lower than that expected by Mendelian ratios
• however, surviving mice show a normal lifespan
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• fertile mice tend to lose their fertility at a younger age than wild-type or heterozygous control mice
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growth/size/body
• embryos show growth retardation during E9.75-E12.5, but not before E9.5 or after E14.5
• at E11.5, embryos show various degrees of growth retardation; by E9.75, almost all embryos exhibit slowed growth
• however, no defects in placental development are observed
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• at E12.5, average body weight is significantly lower than that of control embryos
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embryo
• embryos show growth retardation during E9.75-E12.5, but not before E9.5 or after E14.5
• at E11.5, embryos show various degrees of growth retardation; by E9.75, almost all embryos exhibit slowed growth
• however, no defects in placental development are observed
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• at E12.5, average body weight is significantly lower than that of control embryos
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reproductive system
• at E12.5, primordial germ cells (PGCs) show a significant repression of Nanog, MVH, and Kit expression in the genital ridge, suggesting altered PGC differentiation; however, embryonic gonads exhibit a partial recovery of PGC marker expression at E13.5
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• at E17.5, immunofluorescence analysis using germ-cell markers PGC7 and TRA98 showed decreased numbers of germ cells in the embryonic testis and ovary
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• at 3 months of age, oocyte counts are significantly lower than those in control mice
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• at 2 months of age, seminiferous tubules exhibit severe germ cell loss
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• at 2 months of age, the number of mature epididymal sperm is significantly lower than that in control mice
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• at E11.5, PGC number in the genital ridge is significantly lower than that in control embryos
• however, PGC number is normal in the hindgut at E8.5 and no defects in PGC migration are detected at ~E9.5
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• at E11.5, proliferation of PGCs is significantly decreased in the genital ridge relative to that in control embryos
• however, no difference in PGC apoptosis is observed
|
small ovary
(
J:255491
)
• at 3 months of age, ovaries are significantly smaller than those of control mice
• in contrast, ovary size is normal at E17.5
|
• ovary weight is significantly decreased at 3 months of age
|
• at 2 months of age, the testis is predominantly occupied by degenerated tubules lacking germ cells
|
small testis
(
J:255491
)
• at 1 month of age, testes are significantly smaller than those of control mice
• in contrast, testis size is normal at E17.5
|
• testis weight is significantly decreased at 1 month of age
|
• fertile mice tend to lose their fertility at a younger age than wild-type or heterozygous control mice
|
• 70-80% of females are infertile
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• 70-80% of males are infertile
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cellular
• at E12.5, primordial germ cells (PGCs) show a significant repression of Nanog, MVH, and Kit expression in the genital ridge, suggesting altered PGC differentiation; however, embryonic gonads exhibit a partial recovery of PGC marker expression at E13.5
|
• at E17.5, immunofluorescence analysis using germ-cell markers PGC7 and TRA98 showed decreased numbers of germ cells in the embryonic testis and ovary
|
• at 3 months of age, oocyte counts are significantly lower than those in control mice
|
• at 2 months of age, seminiferous tubules exhibit severe germ cell loss
|
• at 2 months of age, the number of mature epididymal sperm is significantly lower than that in control mice
|
• at E11.5, PGC number in the genital ridge is significantly lower than that in control embryos
• however, PGC number is normal in the hindgut at E8.5 and no defects in PGC migration are detected at ~E9.5
|
• at E11.5, proliferation of PGCs is significantly decreased in the genital ridge relative to that in control embryos
• however, no difference in PGC apoptosis is observed
|
• embryos show a global (whole-body) increase in H3K9 methylation in a developmental stage-dependent manner
• at E9.75, H3K9me2 and H3K9me3 levels are elevated in PGCs and H3K9me3 levels are significantly increased at major satellite repeats
• however, no differences in H3K9 methylation levels are noted after E11.5
|
endocrine/exocrine glands
small ovary
(
J:255491
)
• at 3 months of age, ovaries are significantly smaller than those of control mice
• in contrast, ovary size is normal at E17.5
|
• ovary weight is significantly decreased at 3 months of age
|
• at 2 months of age, the testis is predominantly occupied by degenerated tubules lacking germ cells
|
small testis
(
J:255491
)
• at 1 month of age, testes are significantly smaller than those of control mice
• in contrast, testis size is normal at E17.5
|
• testis weight is significantly decreased at 1 month of age
|
neoplasm
N |
• homozygotes show no changes in the frequency of spontaneous tumorigenesis relative to control mice
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