mortality/aging
• all homozygotes die between E10.5 and E11.5 of cardiovascular insufficiency resulting from atrial malfunction
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cardiovascular system
• by somite pair 24, mutant intersegmental vessels appear disorganized
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• homozygotes display defects in both extraembryonic and intraembryonic vasculature
• by somite pair 24, mutant cranial vessels are less complex and intersegmental vessels appear disorganized
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• at E10.0, mutant yolk sacs show absence of both large and small vessels
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• mutant atrial cardiomyocytes show myofibrillar disorganization, with loss of a normal parallel alignment of thick and thin filaments
• in contrast, cardiomyocytes from the left ventricle display a normal parallel alignment of thick and thin filaments and normal Z-line formation
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• at E10.0-E10.5, homozygtes exhibit a relatively thin walled ventricular myocardium
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• at E10.0-E10.5, homozygotes underdeveloped ventricular trabeculae
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• at E10.0-E10.5, mutant atrioventricular cushions fail to become seeded by mesenchymal cells
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• by somite pair 24-28, homozygotes display enlarged outflow tracts
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• at E10.0-E10.5, mutant atrioventricular cushions fail to grow, suggesting defective septation and valve formation
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• homozygotes display abnormal looping architecture with alterations in the length, shape and size of each cardiac segment, and their geometrical relationship to each other
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• at E8.5 (early linear heart tube stage), homozygotes display enlarged and amorphous hearts, with no clear distinction between the bulbus arteriosus and prospective left ventricle
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• by somite pair 22, homozygotes exhibit enlarged atria
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• at E10.0-E10.5, homozygotes exhibit a dilated left ventricle
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• at E10.5, homozygotes display severe chest edema, indicating heart failure
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• at E9.5, homozygotes exhibit severely reduced atrial beating (44 bpm) relative to wild-type embryos (516 bpm)
• in contrast, ventricular beating remains relatively unaffected (5310 and 487 for wild-type and mutant ventricles, respectively)
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embryo
• at E10.0, mutant yolk sacs show absence of both large and small vessels
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• all homozygotes exhibit growth arrest at approximately somite pair 24-28
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• all homozygotes first exhibit growth retardation at ~E9.0-E9.25 (i.e. 15-17 somite pairs)
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• at E10.0, mutant yolk sacs display separation of the mesodermal and endodermal layers
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• the initial vascular plexus of mutant yolk sacs forms but fails to remodel into a vascular network of larger vessels
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growth/size/body
• all homozygotes first exhibit growth retardation at ~E9.0-E9.25 (i.e. 15-17 somite pairs)
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homeostasis/metabolism
• at E10.5, homozygotes display severe chest edema, indicating heart failure
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muscle
• mutant atrial cardiomyocytes show myofibrillar disorganization, with loss of a normal parallel alignment of thick and thin filaments
• in contrast, cardiomyocytes from the left ventricle display a normal parallel alignment of thick and thin filaments and normal Z-line formation
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• at E10.0-E10.5, homozygtes exhibit a relatively thin walled ventricular myocardium
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• at E10.0-E10.5, homozygotes underdeveloped ventricular trabeculae
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