mortality/aging
• embryos die between E3.5 and E7.5, with morphologically abnormal nuclei detectable as early as the blastocyst stage
• cultured mutant embryos hatch, attach to the culture dish and produce trophoblast giant cells, suggesting that implantation may occur normally
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cellular
• by E3.5, aberrant nuclei with chromatin aggregates or irregularly sized micronuclei are seen; most apparent in the inner region of embryos where rapid cell division occurs
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• initiation of mitosis occurred in mutant embryos despite blocks in DNA replication and DNA damage that normally arrests the cell cycle
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• TUNEL-positive cells are observed in mutant blastocysts, but not in control blastocysts
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• lack of inner cell mass proliferation and failure of generation of homozygous ES cells suggests that this gene product is required for cell proliferation
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• inner cell mass did not grow in cultured mutant embryos
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embryo
• TUNEL-positive cells are observed in mutant blastocysts, but not in control blastocysts
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• lack of inner cell mass proliferation and failure of generation of homozygous ES cells suggests that this gene product is required for cell proliferation
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• inner cell mass did not grow in cultured mutant embryos
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