mortality/aging
• homozygous mutant embryos are detected at a reduced frequency from E2.5 to E3.5; no homozygotes are identified thereafter
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embryo
• homozygous mutant blastocysts are able to hatch from the zona pellucida but fail to form an inner cell mass (ICM) during cellular outgrowth
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• in vitro, homozygous mutant ICMs are completely absent after 6 days in culture; only trophoblastic giant cells are found to persist in long-term cultures
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• in vitro, homozygous mutant ICMs cease proliferating by day 3 of culture and degenerate soon thereafter
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• the number of trophoblast giant cells is significantly decreased in cellular outgrowth of homozygous mutant blastocysts relative to the outgrowth of wild-type blastocysts (10-20 vs 50-150 cells, respectively)
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cellular
• in response to 2 Gy of gamma irradiation, homozygous mutant blastocysts isolated at E3.5 display extensive apoptosis relative to similarly-treated wild-type blastocysts, as revealed by TUNEL analysis
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• in response to 2 Gy of gamma irradiation, homozygous mutant blastocysts isolated at E3.5 display extensive apoptosis relative to similarly-treated wild-type blastocysts, indicating a severe defect in ionizing radiation-induced DNA repair
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• homozygous mutant trophoblast giant cells fail to enter S phase and are arrested in the endocycle, indicating a complete failure of DNA synthesis in giant cells of blastocyst outgrowth
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homeostasis/metabolism
• in response to 2 Gy of gamma irradiation, homozygous mutant blastocysts isolated at E3.5 display extensive apoptosis relative to similarly-treated wild-type blastocysts, indicating a severe defect in ionizing radiation-induced DNA repair
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• homozygous mutant trophoblast giant cells fail to enter S phase and are arrested in the endocycle, indicating a complete failure of DNA synthesis in giant cells of blastocyst outgrowth
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