mortality/aging
• homozygotes die between E9.5 and 10.5 due to defects in the maturation of the yolk sac and chorioallantoic placenta
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growth/size/body
• at E8.5, mutant embryos appear grossly normal but are ~10% smaller than wild-type embryos
• by E9.5, mutant embryos display a number of gross morphological defects and are ~3-fold smaller than wild-type embryos
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embryo
• by E9.5, the number of vitelline vessels is reduced and the vessel walls appear significantly thickened
• only small amounts of blood are detected in these vessels
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• by E9.5, mutant yolk sacs lack a rich nucleated hematopoietic component
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• by E9.5, mutant vitelline vessels appear as a disorganized meshwork lacking organized branching patterns
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• at E9.5, 90% of mutant embryos exhibit no axial rotation; their bodies appear kinked, suggesting that axial rotation is initiated but fails to complete
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• by E9.5, homozygotes exhibit underdeveloped posterior structures, including the posterior limb bud and allantois
• in contrast, the first branchial arch, otic cup, eye primordia, and anterior limb bud, appear developmentally normal
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• at E8.5, mutant embryos appear grossly normal but are ~10% smaller than wild-type embryos
• by E9.5, mutant embryos display a number of gross morphological defects and are ~3-fold smaller than wild-type embryos
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• by E9.5, the mutant posterior limb bud appears underdeveloped relative to wild-type
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• by E9.5, all homozygotes exhibit defects and/or delays in neural tube closure
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• by E9.5, the leading edges which fuse during neural tube closure appear thickened and kinked
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• at E8.5, the allantois fails to fuse with the chorion and appears rounded
• by E9.5, the allantois appears as a bulbous knot
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• by E8.5, mutant yolk sacs already appear thinner and more fragile than normal
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• homozygotes exhibit failure of placental development and maturation
• at E9.5, a significant reduction in BrdU incorporation by trophoblast cells is observed at the chorionic plate adjacent to the area of labyrinthine branching
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• at E8.5, all homozygotes fail to initiate chorioallantoic fusion
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• at E9.5, mutant yolk sacs fail to exhibit a rich mature vascular network
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nervous system
• by E9.5, all homozygotes exhibit defects and/or delays in neural tube closure
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• by E9.5, the leading edges which fuse during neural tube closure appear thickened and kinked
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• by E9.5, mutant hindbrain regions appear underdeveloped relative to wild-type
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• by E9.5, brain development is severely retarded and/or defective
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• by E9.5, mutant forebrain regions appear underdeveloped relative to wild-type
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• by E9.5, mutant midbrain regions appear underdeveloped relative to wild-type
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cellular
• mutant MEFs are viable but exhibit cell cycle defects, including reduced population-doubling time and a delay in cell cycle reentry from quiescence
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• proliferative defects are observed in vivo in the placenta and in vitro in MEFs
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limbs/digits/tail
• by E9.5, the mutant posterior limb bud appears underdeveloped relative to wild-type
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cardiovascular system
• by E9.5, the number of vitelline vessels is reduced and the vessel walls appear significantly thickened
• only small amounts of blood are detected in these vessels
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• by E9.5, mutant yolk sacs lack a rich nucleated hematopoietic component
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• by E9.5, mutant vitelline vessels appear as a disorganized meshwork lacking organized branching patterns
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