mortality/aging
• no homozygous embryos are detected at E15 or E8.5-9.5; absence of resorbed embryos or empty deciduas suggests preimplantation lethality
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embryo
• at E3.5, 70/296 embryos are abnormal, consisting of only eight cells whereas 226/296 had developed into blastocysts consisting of at least 32 cells
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• mutant embryos consist of TGCs that can form 8-cell embryos resembling blastocysts with blastocoelic cavities but lacking inner cell mass (ICM)
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• in mutant embryos, all cells become committed to trophectoderm lineage
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cellular
• nuclei of eight-cell arrested embryos are grossly enlarged and contain three times more DNA than nuclei from wild-type blastocysts at E3.5
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• mutant cells undergo endoreduplication, resulting in >3-fold DNA content in mutant nuclei
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• all cells lose pleuripotency, endoreduplicate, and consist exclusively of differentiated trophoblast giant cells (TGCs)
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