mortality/aging
• no homozygous embryos are found beyond E12.5, although evidence of resorptions is observed; numbers start to decline at E10.5, but are normal up to E9.5
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cellular
• at E10.5, apoptotic cells are increased in number compared to wild-type, especially in the neural tube
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• E9.5 mouse embryonic fibroblast (MEF) cultures have increased numbers of apoptotic cells relative to wild-type MEFs
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• at E10.5
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• proliferating cells are much fewer in number compared to wild-type embryos at E10.5; findings are similar at E9.5
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• E9.5 MEFs cease to grow beyond passage 2-3 in contrast to wild-type cells which grow up to passage 5-6; MEFs exhibit significantly decreased cell proliferation in culture
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embryo
• at E10.5, severe growth retardation is observed
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• at E9.5, some embryos are seen to be smaller than wild-type or heterozygous littermates
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• at E10.5, embryos appear abnormal
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• in some embryos, the neural tube is shrunken
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growth/size/body
• at E10.5, severe growth retardation is observed
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• at E9.5, some embryos are seen to be smaller than wild-type or heterozygous littermates
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nervous system
• at E10.5
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• in some embryos, the neural tube is shrunken
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• proliferating cells marked by Ki-67 labeling are greatly reduced in neuroepithelium at E10.5
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