mortality/aging
• homozygotes die in utero between 10.5 and 12.5 dpc
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cardiovascular system
• at 10.5 dpc, the angiogenic mesenchyme fails to infiltrate the developing labyrinth layer
• by 11.5 dpc, homozygotes exhibit a severely impaired vascular network within the labyrinth, with a nearly complete loss of blood vessels lined with endothelial cells
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• at 10.5 dpc, homozygotes display an angiogenic defect in embryonic and extraembryonic tissues that correlates with impaired placental vascularization
• at 10.5 dpc, mutant brains fail to show angiogenic pruning and remodeling of the vascular plexus, displaying numerous vessels of similar size that are not organized in a branching vascular tree
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cellular
• mutant ES cells show no overt growth or differentiation phenotypes in early embryoid body culture
• notably, attempts to culture primary MEFs are unsuccessful due to cellular inviability following the first passage
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embryo
• by 11.5 dpc, mutant embryos are often developmentally retarded and smaller than wild-type embryos
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• at 10.5 dpc, the mutant placenta appears thinner and paler than normal; however, the chorioallantoic fusion appears unaffected
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• at 10.5 dpc, the angiogenic mesenchyme fails to infiltrate the developing labyrinth layer
• by 11.5 dpc, homozygotes exhibit a severely impaired vascular network within the labyrinth, with a nearly complete loss of blood vessels lined with endothelial cells
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• at 10.5 dpc, homozygotes exhibit a highly abnormal diploid trophoblast with abundant apoptotic cells in the placental labyrinth layer; no differences are noted in the trophoblast giant cell population
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• at 10.5 dpc, the mutant spongiotrophoblast layer is significantly reduced
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• at 10.5 dpc, the developing labyrinth of homozygotes is significantly thinner than that of wild-type embryos
• by 11.5 dpc, the mutant labyrinth layer is essentially absent
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• at 10.5 dpc, mutant visceral yolk sacs lack major blood vessels and retain a primitive capillary plexus
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growth/size/body
• by 11.5 dpc, mutant embryos are often developmentally retarded and smaller than wild-type embryos
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hematopoietic system
N |
• mutant embryos display no gross abnormalities in primitive hematopoiesis or cardiac development
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