mortality/aging
• intercrosses of heterozygotes give rise to viable offspring at the expected Mendelian ratios, with homozygotes appearing phenotypically normal
• notably, mutant embryos develop normally in wild-type mothers carrying homozygous mutant ovary transplants
• however, embryos developing in homozygous pregnant mothers exhibit retardation and lethality, with ~50% and ~70% of conceptuses dead or completely resorbed on E9-E10 an E11, respectively; no living embryos are found after E12
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reproductive system
• on E11, embryos developing in mutant mothers display trophoblast giant cells in the space normally occupied by the decidua capsularis
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• on E6-E8, mutant deciduae are morphologically unremarkable but abnormally small, containing blood-filled lacunae in the antimesometrial region
• on E6-E8, BrdU incorporation in cells of the secondary and mesometrial decidua is significantly reduced, in the absence of increased apoptosis
• on E9, mutant mesometrial and antimesometrial deciduae exhibit progressive degeneration, resulting in complete loss of maternal decidua by E11 in most cases
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• between E6 and E11, homozygous females contain a normal number of implantation sites relative to wild-type females; however, mutant implantation chambers are significantly smaller than wild-type
• notably, homozygous mutant blastocysts transferred into pseudopregnant wild-type females give rise to normal midgestation embryos surrounded by normal implantation sites
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• female homozygotes display reduced fertility due to embryo loss during postimplantation development before E11; embryos successfully develop to term only in rare cases
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• only 3 of 14 test-mated homozygous females give rise to litters with only 1 to 3 pups
• upon continued mating with fertile males over several months, only one female gave rise to two additional small litters
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embryo
• upon mating of homozygous mutant females with wild-type males, uteri of pregnant homozygotes contain either small, hemorrhagic embryos or fully resorbed embryos on E11 and E12
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• embryos developing in mutant mothers display defects in embryo-derived trophectoderm tissue
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• on E11, embryos developing in mutant mothers display trophoblast giant cells in the space normally occupied by the decidua capsularis
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• embryos developing in mutant mothers exhibit only scattered remnants resembling spongio and labyrinthine trophoblast
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• embryos developing in mutant mothers exhibit only scattered remnants resembling spongio and labyrinthine trophoblast
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• embryos developing in mutant mothers exhibit a significantly reduced chorioallantoic placenta, despite normal chorionicallantoic fusion
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• on E6-E8, mutant deciduae are morphologically unremarkable but abnormally small, containing blood-filled lacunae in the antimesometrial region
• on E6-E8, BrdU incorporation in cells of the secondary and mesometrial decidua is significantly reduced, in the absence of increased apoptosis
• on E9, mutant mesometrial and antimesometrial deciduae exhibit progressive degeneration, resulting in complete loss of maternal decidua by E11 in most cases
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growth/size/body
• upon mating of homozygous mutant females with wild-type males, uteri of pregnant homozygotes contain either small, hemorrhagic embryos or fully resorbed embryos on E11 and E12
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immune system
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• female homozygotes exhibit normal thymus and lymph node cells, as well as normal proliferative responses of lymph node cells in response to different doses of B or T-cell mitogens
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