mortality/aging
• mutant embryos fail to develop past E6.5
• by E8.5, most embryos are either in resorption or degenerating within the yolk sac
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embryo
• in vitro, E3.5 mutant blastocysts fail to show ICM proliferation after 6 days in culture
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• mutant embryos fail to progress significantly beyond E5.5 due to a dramatic accumulation of Trp53 protein
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• at E5.5 and esp. at E6.5, mutant embryos are significantly smaller than wild-type embryos
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• at E6.5 , mutant embryos show absence of a developing mesoderm
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• at E6.5, mutant embryos show absence of a primitive streak
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• at E6.5, homozygotes exhibit a poorly defined boundary between the embryonic and extraembryonic regions
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• at E6.5, mutant embryos display a poorly defined parietal endoderm
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• at E5.5, mutant embryos display a poorly defined extraembryonic region
• by E6.5, the extraembryonic region appears severely underdeveloped and disorganized
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• at E5.5, mutant embryos display a disorganized visceral endoderm
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growth/size/body
• at E5.5 and esp. at E6.5, mutant embryos are significantly smaller than wild-type embryos
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cellular
• at E6.5, mutant embryos exhibit a significantly lower mitotic index than wild-type embryos (0.2-0.3 versus 0.7-0.8, respectively)
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• at E6.5, mutant embryos display a significantly reduced cellular proliferation relative to wild-type embryos, as shown by a >40% decrease in BrdU-positive nuclei
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• in vitro, E3.5 mutant blastocysts fail to show ICM proliferation after 6 days in culture
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