Analysis Tools
mortality/aging
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• homozygous null embryos died by E10.5
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cardiovascular system
| N |
• although extraembryonic vascularization was defective, the mutant heart, dorsal aorta and intersomitic vessels appeared normal
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• homozygous null embryos displayed defective angiogenesis of the yolk sac and branchial arches
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• other mutant yolk sacs lacked large vitelline blood vessels and had enlarged capillaries instead
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• in some mutant yolk sacs, there were fewer capillaries and these appeared to be fused with one another generating an abnormal vascular plexus
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cellular
| N |
• mutant ES cells failed to activate genes that normally respond to low oxygen tension (hypoxia)
(J:39730)
• mutant ES cells failed to respond to a decrease in glucose concentration (hypoglycemia)
(J:39730)
• aggregation of mutant ES cells with tetraploid wild-type embryos rescued their placental defects; however, these embryos still died from yolk sac vascular and cardiac defects (reduced endocardial cushions, a hypoplastic ventricular myocardium, an enlarged atrioventricular canal, and distended dorsal aortae)
(J:66515)
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embryo
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• other mutant yolk sacs lacked large vitelline blood vessels and had enlarged capillaries instead
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• at E9.5, mutant embryos appeared developmentally stunted
• notably, individual organ systems appeared morphologically normal relative to wild-type
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• at E9.5, mutant embryos appeared smaller and generally wasted
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• although mutant endothelial cells entered the allantois and chorioallantoic fusion took place, mutant fetal blood vessels failed to invade the chorionic plate by E9.5
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• complete loss of the labyrinthine layer resulted in decreased exchange between maternal and fetal circulations and subsequent intrauterine growth retardation
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• mutant placentas showed poor trophoblast invasion of maternal myometrium, similar to preeclamptic human placentas
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• at E9.5, mutant placentas showed a severe reduction in diploid spongiotrophoblast cell numbers and a significant expansion in the giant cell population
• at E8.5, mutant placentas showed normal numbers of spongiotrophoblast cells that disappeared by E9.5 with no increase in TUNEL+ apoptotic cells, suggesting that spongiotrophoblasts themselves differentiated into giant cells at increased rates
• in contrast to wild-type, homozygous null trophoblast stem (TS) cells cultured under low oxygen tension failed to generate spongiotrophoblasts in vitro
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• at E9.5, mutant placentas showed a severe reduction in diploid spongiotrophoblast cell numbers and a significant expansion in the giant cell population
• at E8.5, mutant placentas showed normal numbers of spongiotrophoblast cells that disappeared by E9.5 with no increase in TUNEL+ apoptotic cells, suggesting that spongiotrophoblasts themselves differentiated into giant cells at increased rates
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• at E9.5, many mutant yolk sacs contained normal blood islands but lacked normal vasculature
• mutant yolk sacs contained a reduced number of surrounding smooth muscle cells in vitelline vessels
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• in some mutant yolk sacs, there were fewer capillaries and these appeared to be fused with one another generating an abnormal vascular plexus
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• mutant placentas contained no fetal vessels and were significantly smaller relative to wild-type
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growth/size/body
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• at E9.5, mutant embryos appeared developmentally stunted
• notably, individual organ systems appeared morphologically normal relative to wild-type
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• at E9.5, mutant embryos appeared smaller and generally wasted
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hematopoietic system
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• as early as E8.5, mutant embryos showed a significant decrease in the number of yolk sac hematopoietic progenitors
• this defect appeared to be cell extrinsic as homozygous null ES cells contributed competitively to all hematopoietic lineages in chimeric mice; also, the defect was associated with a reduction in ARNT-dependent VEGFA expression, and was reversed by exogenous VEGFA
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