mortality/aging
• on a mixed genetic background involving 129/Sv and C57BL/6, homozygous mutant embryos die after gastrulation at E9.0
• an increased number of resorbed and empty conceptuses are observed at E9.5, with no live embryos detected at E10.5
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cardiovascular system
• no maternal blood sinuses are detected in mutant placentas at E10
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• impaired vasculogenesis in the yolk sac at E9.5
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• at E9.5, surviving mutant embryos display an enlarged pericardium
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cellular
• at E9.5, homozygous mutant embryos exhibit massive apoptosis in various regions of the neck and trunk, affecting neural tissues, somites, and endodermal structures
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• as early as E8.0, homozygous mutant embryos display a significantly higher apoptotic cell death within the ectoplacental cone and giant cells relative to wild-type embryos
• in contrast, placental proliferation is not impaired but is mainly restricted to the chorionic plate at E8.0 and to the chorionic stem cells at E9.5
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embryo
• as early as E8.0, homozygous mutant embryos display a significantly higher apoptotic cell death within the ectoplacental cone and giant cells relative to wild-type embryos
• in contrast, placental proliferation is not impaired but is mainly restricted to the chorionic plate at E8.0 and to the chorionic stem cells at E9.5
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• Background Sensitivity: developmental defects exacerbated on C57BL/6 genetic background relative to a mixed background also involving 129/Sv
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• at E9.5, surviving mutant embryos exhibit incomplete embryo turning
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• by E8.5, homozygous mutant embryos exhibit an obvious growth retardation and have only 2-6 somites relative to 8-12 somites observed in wild-type and heterozygous control embryos
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• at E7.5, homozygous mutant embryos are only slightly smaller than wild-type and heterozygous control embryos
• at E8.5, homozygous mutant embryos are only half the size of control embryos
• at E9.5, surviving mutant embryos are significantly smaller than control embryos
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• at E8.0, the entire embryonic cavity of the decidual swelling is smaller than normal
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• at E9.5, the mutant cranial neural plate remains unfused
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• homozygous mutant embryos display defects in extraembryonic tissue formation
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• no maternal blood sinuses are detected in mutant placentas at E10
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• at E9.5, mutant chorionic trophoblast cells fail to differentiate into syncytiotrophoblast cells of the labyrinth
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• at E8.5, the number of trophoblast giant cells is decreased
• only a few giant cells are distributed on top of the invading ectoplacental cone at E9.5
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• at E7.5, the compact cells of the ectoplacental cone are almost absent
• by E8.0, the mutant ectoplacental cone is significantly smaller than normal
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• at E7.5, the extraembryonic ectodermal sheet of the chorion appears to be thinner than normal
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• at E8.0, the mutant chorionic plate is thinner and curved relative to the flat chorionic plate of wild-type placenta
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• no placental labyrinth layer is formed at E9.5
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• vasculogenesis was clearly blocked at E9.5
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• at ~E9.0, the decidual swellings of homozygoys mutant embryos are significantly smaller than normal
• at E8.5, the sizes of the ectoplacental cone and the chorion are strongly reduced, and fewer giant cells observed, while the nuclei and cells of the ectoplacental cone appear to be enlarged
• bt E10.5, the mutant placenta is totally collapsed; only a few giant cells and a thin layer of chorion and spongiotrophoblast cells remain
• no maternal blood sinuses are detected in mutant placentas at E10
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• homozygous mutant embryos exhibit a slight delay in chorioallantoic fusion relative to wild-type embryos (fusion occurs at E8.5 vs E8.0, respectively)
• however, a functional connection of the allantois with the chorion is noted at E9.5
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growth/size/body
• by E8.5, homozygous mutant embryos exhibit an obvious growth retardation and have only 2-6 somites relative to 8-12 somites observed in wild-type and heterozygous control embryos
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• at E7.5, homozygous mutant embryos are only slightly smaller than wild-type and heterozygous control embryos
• at E8.5, homozygous mutant embryos are only half the size of control embryos
• at E9.5, surviving mutant embryos are significantly smaller than control embryos
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nervous system
• at E9.5, the mutant cranial neural plate remains unfused
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integument