mortality/aging
• all die or are moribund by 4 months of age
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• expected numbers are found at birth but by weaning only 6% of mice are homozygous instead of the expected 25%
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cardiovascular system
• disorganized
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• markedly reduced at P7
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• at P7 and P14 cell sizes are strongly increased
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• at E16.5, E18.5 and P2, 30-60% of cardiomyocytes are binucleate while only a small fraction of binucleate cardiomyocytes are found in controls, indicating premature binucleation
• however, at P7 60% of cardiomyocytes are binucleate compared to 90% in wild-type controls
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• slight decrease in the number of cardiomyocytes at E14.5
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• hypertrophic at E18.5 but not at E14.5
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• increase in heart to body weight ratio at P14
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• at 6 weeks of age
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• accompanies changes in cardiac dimensions
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• between E14.5 and P7 cardiomyocytes numbers increase by less than 2-fold compared to over 10-fold in controls
• at E14.5 expression analysis indicates there are fewer mitotic cells and there are fewer cells undergoing cytokinesis
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homeostasis/metabolism
• intracardiac thrombi tightly attached to the ventricular wall are seen in 30% of mice
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liver/biliary system
N |
• proliferation of embryonic hepatocytes is similar to controls
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cellular
• between E14.5 and P7 cardiomyocytes numbers increase by less than 2-fold compared to over 10-fold in controls
• at E14.5 expression analysis indicates there are fewer mitotic cells and there are fewer cells undergoing cytokinesis
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muscle
• disorganized
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• markedly reduced at P7
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• at P7 and P14 cell sizes are strongly increased
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• at 6 weeks of age
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• accompanies changes in cardiac dimensions
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• between E14.5 and P7 cardiomyocytes numbers increase by less than 2-fold compared to over 10-fold in controls
• at E14.5 expression analysis indicates there are fewer mitotic cells and there are fewer cells undergoing cytokinesis
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growth/size/body
• increase in heart to body weight ratio at P14
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