mortality/aging
• surprisingly, homozygous mutant embryos die at mid-gestation, exhibiting a significant decline in Mendelian frequency between E9.5 and E12.5
• attempts to generate homozygous mutant ES cells and embryonic fibroblasts from mid-gestation embryos have been unsuccessful
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embryo
• mutant embryos show reduced branching of blood vessels in the yolk sac
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• mutant embryos fail to turn by E9.5; however, some mutants are able to complete axial rotation by E10.5
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• at E9.5-E12.5, homozygous mutant embryos display a developmental delay of up to 2 days relative to wild-type embryos
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• starting at E8.5, homozygous mutant embryos appear smaller than their heterozygous and wild-type counterparts
• at E9.5-E12.5, homozygous mutant embryos are ~60% of wild-type length
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• at E10.5, mutant embryos display a highly disorganized and degenerated mesenchyme, with pyknotic bodies and debris detected throughout the tissue
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• epithelial and neuroepithelial cell pleiomorphism is commonly observed
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• at E10.5, mutant embryos display degeneration of neural tube tissue
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• at E9.5 and E10.5, homozygous mutant somites display a diffuse, aberrant structure
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• at E9.5 and E10.5, homozygous mutant embryos have decreased numbers of somite pairs relative to heterozygous embryos
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• mutant yolk sacs are often fragile, with loose attachment of the embryo to the decidual implantation site, possibly due delayed and/or inadequate chorioallantoic fusion
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nervous system
• epithelial and neuroepithelial cell pleiomorphism is commonly observed
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• at E10.5, mutant embryos display degeneration of neural tube tissue
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cardiovascular system
• mutant embryos show reduced branching of blood vessels in the yolk sac
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• at E10.5 or later, mutant embryos exhibit pericardial sac edema
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cellular
• homozygous mutant embryos display widespread degeneration and cell death
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craniofacial
homeostasis/metabolism
• at E10.5 or later, mutant embryos exhibit pericardial sac edema
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growth/size/body
• at E9.5-E12.5, homozygous mutant embryos display a developmental delay of up to 2 days relative to wild-type embryos
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• starting at E8.5, homozygous mutant embryos appear smaller than their heterozygous and wild-type counterparts
• at E9.5-E12.5, homozygous mutant embryos are ~60% of wild-type length
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