mortality/aging
• no homozygotes survive beyond E15.5 as a result of heart failure
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• starting at E9, homozygotes exhibit a progressive decline in embryonic survival up to E15.5
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cardiovascular system
• at E12.5-E15.5, homozygotes display abnormally thinned trabeculae in the ventricles and atria
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• at E12.5-E15.5, homozygotes display an abnormally thin compact myocardial layer
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• at E12.5-E15.5, homozygotes exhibit absence of organization or differentiation of the ventricular myocardium
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• at E12.5-E15.5, homozygotes display hypoplasia of the right and left atria
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• at E13, homozygotes display a dilated right atrium
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• at E12.5-E15.5, homozygotes display hypoplasia and dysplasia of the interventricular septum, with persistence of an aberrantly wide interventricular foramen
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• at E12.5-E15.5, homozygotes display hypoplasia and dysplasia of the myocardium
• mutant ventricular and atrial cavities (lumina) appear unusually large as a result of hypoplasia
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• at E12.5-E15.5, homozygotes display hypoplasia of both the right and left ventricles
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• at E12.5-E15.5, homozygotes show disorganized trabeculae in the ventricular wall
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• in some homozygotes, the nontrabeculated ventricular myocardium is composed of only a single cell layer; in contrast, the endocardial and epicardial layers appear normal
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• at E12.5-E13.5, homozygotes display a >70% decrease in left ventricular ejection fraction, indicating ventricular chamber dysfunction
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growth/size/body
• at E15.5, homozygotes display an overall developmental delay of ~24-36 hr relative to wild-type embryos
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muscle
• at E12.5-E15.5, homozygotes display abnormally thinned trabeculae in the ventricles and atria
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• at E12.5-E15.5, homozygotes show disorganized trabeculae in the ventricular wall
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• at E12.5-E15.5, homozygotes display an abnormally thin compact myocardial layer
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• at E12.5-E15.5, homozygotes exhibit absence of organization or differentiation of the ventricular myocardium
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• at E12.5-E13.5, homozygotes display a >70% decrease in left ventricular ejection fraction, indicating ventricular chamber dysfunction
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embryo
integument
• at E15.5, homozygotes exhibit a normal liver but are generally paler than wild-type or heterozygous embryos, suggesting inadequate vascular irrigation
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