mortality/aging
• ~50% of homozygous mutant embryos die before implantation
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• no homozygous mutant embryos are detected at E7.5; instead, only completely absorbed embryonic tissues are identified in the decidua
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embryo
• at E5.5, mutant but not wild-type embryos undergo selective apoptosis of the inner cell mass
• notably, mutant trophoblastic cells escape apoptosis and remain viable as late as E6.5
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• ~50% of homozygous mutant embryos show defective blastocyst formation
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• ~50% of homozygous mutant embryos display defects in hatching
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• at E6.0, most mutant embryos consist of extraembryonic tissue
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• at E6.0, most mutant embryos lack an embryonic ectoderm
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• at E6.0-E6.5, remaining mutant embryos appear disorganized and lack the cylinder-like two-layered cellular structure observed in wild-type embryos
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• an atrophic inner cell mass is observed
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cellular
• mutant trophoblastic cells cannot enter the S phase of the endoreduplication cycle
• this cell cycle arrest is accompanied with elevated expression of cyclin E and p57Kip2, suggesting that both mitotic and the endoreduplicative cell cycle progression are affected
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• at E5.5, mutant but not wild-type embryos undergo selective apoptosis of the inner cell mass
• notably, mutant trophoblastic cells escape apoptosis and remain viable as late as E6.5
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