Analysis Tools
mortality/aging
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• partial loss of homozygotes observed at mid-gestation and after birth, with 17% obtained at E13.5 and 13.3% at P7
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growth/size/body
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• at E12.5
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• from P7 through adulthoood
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• significant reduction in body weight at 6 months
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• from P2 to P14
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• postnatal growth retardation persists into adulthoood
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• at E17.5
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reproductive system
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• PGCs are unable to make the developmental transition from E7.5 to E9.5
• however, specification of PGCs is normal
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• progressive decrease in PGC number starting at the late head fold stage, with a drastic reduction from E8.5 onward and only few PGCs found in the hindgut endoderm at E9.0
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• no PGCs detected at E9.5 and E10.5
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• absence of germ cells in ovaries (P80) as well as in testes and epididymi (P70)
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• TUNEL analysis revealed some SSEA1-positive PGCs undergoing cell death in E9.0 hindgut endoderm, indicating apoptosis of PGCs early after specification
• however, no activation of DNA damage response is noted in apoptotic PGCs
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• emigration to the dorsal mesentery fails to occur; as a result, gonad primordia are devoid of germ cells at E13.5
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• at P80, ovaries are either not formed at all or appear as small organ rudiments that do not contain ovarian follicles or germ cells
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• absence of ovarian follicles in small ovaries
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small ovary
(
J:223048
)
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• one small ovary without follicles in 3 of 12 females
• two small ovaries without follicles in 2 of 12 females
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absent ovary
(
J:223048
)
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• failure to generate ovaries in 7 of 12 females
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• lack of spermatogonial cells, pre-meiotic cells, and meiotic cells in seminiferous tubules at P14
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• highly vacuolated Sertoli cells at P70
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• misslocalized Sertoli cells at P70
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• at P70
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small gonad
(
J:223048
)
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• significantly underdeveloped gonads
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small testis
(
J:223048
)
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• drastically smaller testes at P70
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cellular
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• PGCs are unable to make the developmental transition from E7.5 to E9.5
• however, specification of PGCs is normal
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• progressive decrease in PGC number starting at the late head fold stage, with a drastic reduction from E8.5 onward and only few PGCs found in the hindgut endoderm at E9.0
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• no PGCs detected at E9.5 and E10.5
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• absence of germ cells in ovaries (P80) as well as in testes and epididymi (P70)
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• at E9.0, most Oct4-positive PGCs fail to arrest in the G2 phase of the cell cycle; cyclin B1 protein is either localized in the nucleus (37%,), in the cytoplasm (39.3%) or not present at all (23.66%) suggesting active cycling, unlike in wild-type PGCs which show cytoplasmic staining (90.9%)
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• TUNEL analysis revealed some SSEA1-positive PGCs undergoing cell death in E9.0 hindgut endoderm, indicating apoptosis of PGCs early after specification
• however, no activation of DNA damage response is noted in apoptotic PGCs
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• emigration to the dorsal mesentery fails to occur; as a result, gonad primordia are devoid of germ cells at E13.5
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• PGCs are unable to make the epigenetic transition from H3K9me2 state at E7.5 to H3K27me3 state at E9.5
• at E9.0, most Oct4-positive PGCs fail to downregulate the repressive histone H3K9me2 whereas most wild-type PGCs have lost this histone modification; two H3K9 methyltransferases, G9a and GLP, are still found in mutant, but not in wild type PGCs
• by E9.0, many PGCs fail to upregulate H3K27me3 above the basal level in somatic cells, likely due to presence of inactive phosphorylated Ezh2 in 60% of PGCs
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embryo
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• at E12.5
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endocrine/exocrine glands
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• at P80, ovaries are either not formed at all or appear as small organ rudiments that do not contain ovarian follicles or germ cells
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• absence of ovarian follicles in small ovaries
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small ovary
(
J:223048
)
|
|
• one small ovary without follicles in 3 of 12 females
• two small ovaries without follicles in 2 of 12 females
|
absent ovary
(
J:223048
)
|
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• failure to generate ovaries in 7 of 12 females
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• lack of spermatogonial cells, pre-meiotic cells, and meiotic cells in seminiferous tubules at P14
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• highly vacuolated Sertoli cells at P70
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• misslocalized Sertoli cells at P70
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• at P70
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small testis
(
J:223048
)
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• drastically smaller testes at P70
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