growth/size/body
• surviving mutants exhibit higher heart/body weight ratio at 3 months of age and increased expression of hypertrophy-related genes
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mortality/aging
• only 15 of 172 F2 generation mutants survive to adulthood
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• most F2 generation mutants die by E16.5
• no live mutants are generated following the F2 and F3 crosses
• 15 of 172 F2 generation mutants survive to adulthood
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cardiovascular system
• increase in the size of cardiac myocytes at 3 months of age
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• at E11.5, cardiac myocytes do not invade the underlying cardiac cushions, indicating defective myocardialization of the developing outflow tract
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• impaired cytokinesis of cardiac myocytes, showing increased binucleation
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• cardiac myocytes are decreased by 70% compared to controls at E16.5
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• cardiac myocytes are enlarged at E13.5
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• 5 of 7 F3 generation mutants between E13.5 and E16.5 have dextroposition of the aorta resulting in a double outlet right ventricle (DORV)
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• 7 of 7 F3 generation mutants between E13.5 and E16.5 have a ventricular septal defect (VSD)
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• surviving mutants exhibit higher heart/body weight ratio at 3 months of age and increased expression of hypertrophy-related genes
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• surviving mutants show presence of interstitial fibrosis in the heart at 3 months of age
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• surviving mutants do not exhibit ventricular septal defect or double outlet right ventticle, however starting at 3 month of age, they show signs of dilated cardiomyopathy
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• 3 month old hearts show a decrease in fractional shortening and an increase in the end systolic and diastolic dimensions
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muscle
• increase in the size of cardiac myocytes at 3 months of age
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• surviving mutants do not exhibit ventricular septal defect or double outlet right ventticle, however starting at 3 month of age, they show signs of dilated cardiomyopathy
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• 3 month old hearts show a decrease in fractional shortening and an increase in the end systolic and diastolic dimensions
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nervous system
N |
• no evidence of hydrocephalus as seen in Myh10tm2Rsad mice
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• facial and pontine neurons migrate abnormally and the former protrudes into the fourth ventricle
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• minor alterations in the foliation pattern at E16.5
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cellular
• surviving mutants show presence of interstitial fibrosis in the heart at 3 months of age
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• facial and pontine neurons migrate abnormally and the former protrudes into the fourth ventricle
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