mortality/aging
• number of homozygous embryos at E11.5 is lower than expected and none are recovered at E12.5 or later
• some embryos die in the middle of turning (prior to E10)
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cardiovascular system
• at E10, embryos lack fine capillary network in the cranial, branchial, cardiac and intersomitic regions
• extracellular matrix (ECM) deposition is aberrant around endothelial cells, impairing migration
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• at E10, smooth muscle cells are lacking around the dorsal aorta; endothelial cells in mutant dorsal aortae are not supported by mural cells, resulting in collapse of the dorsal aorta
• tight junctions between endothelial cells form normally
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• yolk sac vasculature is formed in mutant yolk sacs, but is highly dilated
• at E10, yolk sac shows primary capillary plexus, but no branching from pre-existing vessels
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• at E10, some homozygotes show an enlarged pericardium and clumps of red blood cells
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cellular
• most mutant mesenchymal nuclei are irregularly shaped compared to wild-type nuclei which are tense and smooth; some mesenchymal cells display herniated nuclei and a small frequency (~1%) have expanded perinuclear space
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• massive apoptosis is detected in homozygous embryos, particularly in mesenchymal tissues, compared to wild-type littermates
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embryo
• yolk sac vasculature is formed in mutant yolk sacs, but is highly dilated
• at E10, yolk sac shows primary capillary plexus, but no branching from pre-existing vessels
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• massive apoptosis is detected in homozygous embryos, particularly in mesenchymal tissues, compared to wild-type littermates
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• at E10, homozygous embryos have smaller, paler yolk sacs
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