mortality/aging
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• seven of 28 mice collected at P0 at dead
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cardiovascular system
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• at P0, the right ventricle (RV) myocardium shows an absence of long F-actin filaments
• at E13.5, active (non-phosphorylated) beta-catenin staining between cell junctions is decreased in the RV myocardium
• at E13.5, mRNA levels of several transcription factors involved in heart development (Gata4, Nkx2.5, Tbx5 and Hand2) are significantly decreased in the RV myocardium
• however, Tbx20 mRNA levels are normal in the RV at E13.5
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• at P0, the right ventricle (RV) myocardium shows poor trabeculation
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• at P0, the RV compact myocardium is significantly thinner than in control hearts
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• at P0, RV cardiomyocytes appear rounded (spherically shaped) and exhibit defective polarity with loss of long F-actin filaments; active beta-catenin staining at cell-cell junctions is decreased at E13.5, suggesting reduced cell adhesion
• at E12.5 and E15.5, expression of SCRIB (scribble planar cell polarity protein) is almost absent in the RV and interventricular septum junction, supporting a failure of cardiomyocytes to undergo polarization
• in culture, neonatal cardiomyocytes show disrupted actin organization, absence of distinct cell projections, and a significantly shorter long-axis length; >40% of cardiomyocytes are rounded, whereas control cardiomyocytes are elongated
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• at P0, all hearts (28 of 28) exhibit a deep interventricular groove and a bifurcation between the right (RV) and the left ventricle (LV), indicating a bifid cardiac apex
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• at P0, 82% (23 of 28) of hearts show atrial septal defects
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• formation of the interventricular septum is impaired: a deep fissure between the RV and LV is first seen at E11.5 and persists as a deep cleft separating the ventricles by E15.5
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• at P0, all hearts (28 of 28) exhibit ventricular septal defects
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• at E13.5, transcriptional regulation of RV development is severely disrupted
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• at P0, all hearts (28 of 28) exhibit a deep interventricular groove
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cellular
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• at E13.5, the RV of the heart shows decreased active (non-phosphorylated) beta-catenin staining between cell junctions
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• at E11.5, cleaved caspase-3 staining shows significantly higher levels of apoptosis in the RV and the interventricular septum, but not in the LV, of the heart
• however, no differences in cell proliferation are detected in E11.5 heart sections
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muscle
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• at P0, the right ventricle (RV) myocardium shows an absence of long F-actin filaments
• at E13.5, active (non-phosphorylated) beta-catenin staining between cell junctions is decreased in the RV myocardium
• at E13.5, mRNA levels of several transcription factors involved in heart development (Gata4, Nkx2.5, Tbx5 and Hand2) are significantly decreased in the RV myocardium
• however, Tbx20 mRNA levels are normal in the RV at E13.5
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• at P0, the right ventricle (RV) myocardium shows poor trabeculation
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• at P0, the RV compact myocardium is significantly thinner than in control hearts
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