All Phenotypes Mtfp1<tm1.2Wait> MGI Mouse

premature death ( J:330965 )

• significantly shorter lifespans, 26.4 weeks and 37.5 weeks for males and females, respectively

pulmonary vascular congestion ( J:330965 )

• in mice with severe heart failure

enlarged heart ( J:330965 )

• increased mass in mice with severe heart failure

thin interventricular septum ( J:330965 )

• thinning during systole

dilated heart left ventricle ( J:330965 )

• during diastole and systole

thin ventricular wall ( J:330965 )

• wall thinning at 34 weeks of age

cardiac fibrosis ( J:330965 )

• in symptomatic mice

dilated cardiomyopathy ( J:330965 )

• progressive decrease in systolic function starting at 18 weeks of age culminating in dilated cardiomyopathy and left ventricular remodeling

• decreased left ventricular ejection fraction by 34 weeks of age

• prior to onset of cardiomyopathy (8-10 weeks of age) no significant difference in cardiomyocyte excitation-contraction coupling is seen

increased cardiomyocyte apoptosis ( J:330965 )

• increased cell death when exposed to H2O2 or doxorubicin in culture and to doxorubicin in vivo

abnormal mitochondrial physiology ( J:330965 )

• impaired mitochondrial O2 consumption in hearts at early and late stages of dilated cardiomyopathy

• significant reduction in complex I-, complex II- and complex IV-driven mitochondrial respiration

• no changes in mitochondrial protein content or markers of mitochondrial metabolic activity in pre-symptomatic mice

• respiration is about 30% higher in cardiac mitochondria in state 2 and state 4 when complex 1 is fueled by pyruvate, malate, glutamate

• results indicate increase in proton leak in cardiac cells

• increased mitochondrial swelling in response to high concentrations of Ca2+ induced opening of the mitochondrial permeability transition pore

• increased cardiac dysfunction and acceleration of the onset of cardiomyopathy in response to doxorubicin