mortality/aging
• no homozygous pups were identified among 900 postnatally genotyped progeny of heterozygous
intercrosses
• although at E9.5, embryonic genotypes occur in the expected Mendelian ratios, only two, partly resorbed homozygous embryos were observed at E10.5
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embryo
• at embryonic day E7.5, about 50% of homozygous embryos exhibit some morphologic abnormality, the rest appearing normal; by E8.5, all mutant embryos have a characteristic phenotype
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• midline expression of brachyury (T) in E8.5 mutant embryos occurs in a wide, discontinuous band rather than the narrow, defined band seen in wild-type controls, indicating abnormal development along the mediolateral axis
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• E9.5 mutant embryos have failed to turn, retaining the distal point, the bend point of the unturned body axis
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• at E8.5, mutant embryos have a strikingly short, wide body axis; by E9.5, failure of elongation of the body axis is even more pronounced
• homozygous mutant E8.5 embryos exhibit caudal dysgenesis
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• all mutant embryos are very small at E9.5
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• at E8.5, mutant embryos have a strikingly short, wide body axis; by E9.5, failure of elongation of the body axis is even more pronounced
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• at E8.5, histologic examination reveals that homozygous embyros have failed to maintain the posterior epiblast-like epithelium in the streak region; the tissue layer overlying the mesoderm is thinner than normal
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• perturbations observed in E7.5 mutant embryos include a marked constriction at the embryonic-extraembryonic boundary or total separation of the epiblast from the extraembryonic ectoderm
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• histologic examination of E7.5 homozygous embryos reveals disorganization of the yolk sac mesoderm
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• although both endothelial cells and erythroblasts, which together normally comprise the yolk sac vasculature, are abundant in the E8.5 mutant yolk sac, they have not organized to form the primitive vascular plexus
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• yolk sac visceral endoderm-adjacent mesoderm of mutant E7.5 embryos lacks the organization characteristic of early blood island development
• although mesoderm cells are abundant in E8.5 mutant yolk sac, few defined blood-island-like structures are evident, and endothelial and hematopoietic precursor cells are not clearly distinguishable
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• at E9.5, yolk sacs of mutant embryos have a distinctively rippled appearance
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growth/size/body
• all mutant embryos are very small at E9.5
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• ventral closure has failed to occur in mutant embryos by E9.5
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cardiovascular system
• although blood vessels are present in the embryo proper at E8.5, their positioning is aberrant
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• although both endothelial cells and erythroblasts, which together normally comprise the yolk sac vasculature, are abundant in the E8.5 mutant yolk sac, they have not organized to form the primitive vascular plexus
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nervous system
• mutant embyos at E8.5 exhibit multiple folding, and E9.5 embryos convolution, of the anterior eptithelium
• histologic examination of E8.5 homozygous embryos reveals excessive folding of the neurectoderm, which extends as a single tissue layer into the amniotic cavity
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