mortality/aging
• all homozygotes die by E11
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embryo
• at E9.5, intercalation bidirectional growth of arteries and veins in the yolk sac is absent in mutants across the anterior-posterior compared to heterozygous controls
• defects in yolk sac angiogenesis are apparent at 9.0, becoming prominent at E9.5
• in the anterior region of the yolk sac, there is a block to remodeling at the capillary plexus stage for arterial and venous vessels at E9-9.5
• support cells in mutants are more rounded in appearance in contrast to the elongated support cells associated with the endothelial vessels in control heterozygotes at E10 and 10.5
• in contrast to heterozygote yolk sacs, capillary diameter appears relatively uniform between E9.5 through E10.5 rather than increasing; mutant capillaries fail to delaminate from the basal endodermal layer
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• apparent by E10
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growth/size/body
• heart is enlarged in E10 embryos
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• apparent by E10
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cardiovascular system
N |
• formation of major vessels in the trunk of the embryo is normal
• iintersomitic vessels originating from the dorsal aorta form normally at E9.5
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• embryonic angiogenesis is defective such that the capillary bed in the heads of mutant embryos appears dilated and apparently arrested at the primary plexus stage
• anterior-most branches of the internal carotid artery fail to develop
• capillary ingrowth into the neural tube fails to occur; endothelial cells remain associated with the surface of the developing spinal cord
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• anterior branches of the anterior cardinal vein form but are slightly dilated
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• at E9.5, intercalation bidirectional growth of arteries and veins in the yolk sac is absent in mutants across the anterior-posterior compared to heterozygous controls
• defects in yolk sac angiogenesis are apparent at 9.0, becoming prominent at E9.5
• in the anterior region of the yolk sac, there is a block to remodeling at the capillary plexus stage for arterial and venous vessels at E9-9.5
• support cells in mutants are more rounded in appearance in contrast to the elongated support cells associated with the endothelial vessels in control heterozygotes at E10 and 10.5
• in contrast to heterozygote yolk sacs, capillary diameter appears relatively uniform between E9.5 through E10.5 rather than increasing; mutant capillaries fail to delaminate from the basal endodermal layer
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• marker analysis indicates that ventricular myocardial differentiation is impaired
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• at E10, myocardial trabecular extensions are absent
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• between E8.5 and 9 primitive endocardium is only mildly perturbed compared to controls
• at E10, the endocardium shows pronounced disorganization
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• heart is enlarged in E10 embryos
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• marker analysis indicates that ventricular myocardial differentiation is impaired
• however, ventricular cell proliferation is normal
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muscle
• marker analysis indicates that ventricular myocardial differentiation is impaired
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• at E10, myocardial trabecular extensions are absent
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