Analysis Tools
mortality/aging
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• a few homozygotes survive to P13; no viable homozygotes are recovered at weaning age
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• although viable homozygous embryos are present at Mendelian ratios at E10.5 and E13.5, most homozygotes die shortly after birth due to heart failure
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growth/size/body
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• at P0-P13, body weight is significantly lower than in control littermates
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cardiovascular system
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• at E13.5, trabeculae are morphologically distinct and not yet compacting
• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae
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• at P0, P5 and P7, ventricles show myocardial hypoplasia
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• transcriptome analysis shows altered transcriptional networks in both atria and ventricles at P3
• at E13.5, hearts show extracellular matrix (ECM) remodeling, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)
• at E13.5, surface expression of Jag1 (jagged 1) on myocardial (Vcam1+) cells is reduced, leading to altered Notch1 signaling and heart development
• however, no defects in proliferation are noted in the atria or ventricles and no increased cell death is detected at E13.5
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• at P0, P5 and P7, atria are severely enlarged
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• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae
• the fibrotic area is significantly increased in both the atria and ventricles relative to control mice
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• at E13.5, mice exhibit an intraventricular shunt (IVS), whereas ventricles are already fully septated in control embryos
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• homozygotes die shortly after birth due to heart failure
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cellular
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• at E13.5, hearts show extracellular matrix (ECM) accumulation, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)
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muscle
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• at E13.5, trabeculae are morphologically distinct and not yet compacting
• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae
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• at P0, P5 and P7, ventricles show myocardial hypoplasia
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