mortality/aging
• homozygous mutant embryos die by E10.5
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embryo
• at E8.5, homozygotes exhibit excessive apoptosis in the embryo proper, esp. at the distal tip
• at E9.5, mutant embryos display large regions of TUNEL+ cells in both ectodermal and mesodermal tissues
• excessive apoptosis occurs predominantly in the embryo proper and not typically in the extraembryonic tissues (e.g. parietal cells are TUNEL-)
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• at E9.5, homozygous mutant embryos are always unturned
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• at E7.5, severely affected homozygotes display a reducion of all three germ layers, with mesoderm formation being most affected
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• at E7.5, many homozygotes display fewer mesodermal cells relative to the embryo size; in addition, cells appear to be more closely packed
• by E8.5, some homozygotes display better epiblast cavity expansion and form mesoderm derivatives such as heart and somites but still lag behind in development, being only 50% of wild-type size
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• at E9.5, homozygotes exhibit a relatively underdeveloped, undersized posterior axis
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• at E8.5, homozygotes are developmentally retarded by one day relative to wild-type or heterozygous embryos
• at E10.5, homozygotes are identical to E9.5 homozygotes, but have begun to deteriorate
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• at E8.5, some homozygotes are only 50% of wild-type size
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• at E7.5, extraembryonic structures are often not delayed to the same extent as the embryo proper; however, the decidual cavities are typically distorted and reduced both in length and width
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• at E9.5, homozygotes display a hydroponic allantois, suggesting an improper chorioallantoic fusion
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• at E7.5, extraembryonic structures are often not delayed to the same extent as the embryo proper; however, the exocoelomic cavity is often malformed
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• at E7.5, parietal endoderm cells fail to spread on Reichert's membrane and their nuclei appear to be denser than normal
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• at E7.5, homozygotes exhibit a thickened Reichert's membrane
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• at E7.5, homozygotes exhibit abnormal epiblast cavity formation
• by E8.5, some homozygotes display better epiblast cavity expansion
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• at E9.5, homozygotes display a hydroponic allantois, suggesting an improper chorioallantoic fusion
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• at E8.5, homozygotes display a discontinuous, usually thicker visceral endoderm layer, with enlarged apical vacuoles
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growth/size/body
• at E8.5, homozygotes are developmentally retarded by one day relative to wild-type or heterozygous embryos
• at E10.5, homozygotes are identical to E9.5 homozygotes, but have begun to deteriorate
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• at E8.5, some homozygotes are only 50% of wild-type size
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cellular
• at E9.5, homozygotes exhibit impaired N-glycosylation of multiple embryonically expressed proteins, such as laminin gamma 1, laminin beta and alpha-fetorprotein
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• at E8.5, homozygotes exhibit excessive apoptosis in the embryo proper, esp. at the distal tip
• at E9.5, mutant embryos display large regions of TUNEL+ cells in both ectodermal and mesodermal tissues
• excessive apoptosis occurs predominantly in the embryo proper and not typically in the extraembryonic tissues (e.g. parietal cells are TUNEL-)
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homeostasis/metabolism
• at E9.5, homozygotes display a hydroponic allantois, suggesting an improper chorioallantoic fusion
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