mortality/aging
• lethality occurs after E12.5; at E13.5, ~70% of homozygous embryos are dead, and no viable embryos are found after E14.5 (with lethality resulting from cardiac failure)
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embryo
• at E12.5, placenta edge is fuzzy and patchy red spots are observed
• enlarged intervillous spaces are abundant at E11.5, but less obvious at E10.5
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• abnormal distribution begins at E10.5 and is apparent by E11.5
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• near center of placenta, number of giant cells is significantly reduced in nulls (4.2) vs wild-type (11.2)
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• distribution is abnormal by E11.5; compared to normal littermates, where most cells are in layer between labyrinth and giant cells, there is significant invasion of spongiotrophoblasts into placental labyrinth
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• labyrinths contain sparse populations of villi, accompanied by large empty spaces (enlarged intervillous maternal lacunae)
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• at E13.5, embryos are often found dead with pale yolk sacs
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cardiovascular system
• at E13.5, dead embryos often have a dark redness around the heart and abdominal region, possibly due to erythrocyte congestion
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• at E12.5, heart development is dramatically retarded compared to heterozygotes or wild-type
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• at E12.5 both atria are enlarged and congested with erythrocytes
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• compact layer of ventricles is much thinner than in normal littermates
• intraventricular lumen is enlarged
• ventricular walls are slightly thinner at E11.5 than in normal littermates, becoming much more obvious by E12.5
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• at E12.5, trabeculae are underdeveloped
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• at E12.5, the compact layer of ventricles is much thinner than in normal littermates
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• at E12.5, interventricular septum is not completely closed whereas it is closed in wild-type at this time
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• defective ventricle formation results in cardiac failure
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immune system
• at E12.5, jugular lymph sacs are dilated
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muscle
• at E12.5, trabeculae are underdeveloped
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• at E12.5, the compact layer of ventricles is much thinner than in normal littermates
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