All Phenotypes Hira<tm1c(EUCOMM)Wtsi> MGI Mouse

• hearts show re-expression of fetal cardiac genes

• however, heart development proceeds normally

abnormal myocardial fiber morphology ( J:231593 )

• hypertrophic cardiomyocytes are seen in the right ventricle free wall as early as 15 days after birth

• however, aberrant proliferation of or apoptosis of cardiomyocytes is not seen and there is no evidence of increased DNA damage

myocardial fiber degeneration ( J:231593 )

• lesions contain degenerating cardiomyocytes

cardiac fibrosis ( J:231593 )

• hearts at 6 weeks and 6 months of age exhibit white surface scars localized to the subepicardial region of the ventricular free walls; lesions contain degenerating cardiomyocytes and a large degree of collagen deposition indicating focal replacement fibrosis localized to the subepicardial myocardium

abnormal cardiovascular system physiology ( J:231593 )

• mice show increased arterial elastance at 6 months of age, which is a measure of arterial load

• the slope of the end-diastolic pressure-volume relationship, which describes diastolic function, is elevated

• however, no effect is seen on the slope of end-systolic pressure-volume relationship, which describes the maximal developed ventricular pressure at any given ventricular volume

abnormal blood circulation ( J:231593 )

• mice show decreased stroke work at 6 months

decreased cardiac output ( J:231593 )

• at 6 months of age

decreased cardiac stroke volume ( J:231593 )

• at 6 months of age

abnormal cardiac muscle contractility ( J:231593 )

• mice exhibit increased dp/dtmax-end-diastolic volume, the relationship between peak rate of pressure rise and EDV, which describes ventricular contractile performance

abnormal myocardial fiber physiology ( J:231593 )

• mice show an increase in diastolic myocardial stiffness

congestive heart failure ( J:231593 )

oxidative stress ( J:231593 )

• levels of manganese superoxide dismutase are reduced in scar-containing free-wall right ventricle, but not in non-scarred regions, suggesting impaired response to oxidative stress

• however, only very minor increases in reactive oxygen species are seen, indicating that cardiomyocyte degeneration most likely is not caused by increased oxidative stress