Phenotypes Associated with This Genotype

Genotype
MGI:5907992

• Allelic Composition: Sod2^tm1Shs/Sod2^tm1Shs; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6CrSlc * FVB

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:117386 )

• some mice begin to die at 8 weeks of age, and all mice die by 22 weeks of age, with a median survival rate of 15.4 weeks

growth/size/body

enlarged heart ( J:117386 )

• all mice show cardiac enlargement at 16 weeks of age

increased heart weight ( J:117386 )

• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months

decreased body weight ( J:117386 )

• mice show a 25% reduction in body weight at 16 weeks of age, without muscle atrophy

postnatal growth retardation ( J:117386 )

• mice begin to exhibit growth retardation at 8 weeks of age

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:117386 )

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

abnormal myocardium layer morphology ( J:117386 )

• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei

myocardial fiber degeneration ( J:117386 )

• left ventricular wall shows myocardial degeneration

• however, apoptotic cell death is not seen in myocardium or skeletal muscle

cardiac muscle necrosis ( J:117386 )

• some of the fibrotic foci are due to necrotic changes of the myocardium

enlarged heart ( J:117386 )

• all mice show cardiac enlargement at 16 weeks of age

increased heart weight ( J:117386 )

• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months

abnormal heart left ventricle morphology ( J:117386 )

• left ventricular wall shows small mitochondria associated with scattered abnormal vacuoles

dilated heart ventricle ( J:117386 )

• dilation of both left and right ventricles

dilated heart left ventricle ( J:117386 )

• the left ventricular end-diastolic and end-systolic diameters are increased indicating left ventricular dilation

cardiac interstitial fibrosis ( J:117386 )

• diffuse fibrotic scars surround myocardial cells

• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles

dilated cardiomyopathy ( J:117386 )

• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:117386 )

• cardiac contractility is depressed in 2 and 4 month old mice as assessed by fractional shortening and ejection fraction

• mice administered the antioxidant manganese 5, 10, 15, 20-tetrakis (4-benxoic acid) porphyrin (MnTBAP) exhibit improvement in cardiac function but no effect on heart weight

abnormal heart echocardiography feature ( J:117386 )

• the left ventricular end-diastolic and end-systolic diameters are increased at 2 and 4 months of age indicating left ventricular dilation

• however, diastolic intraventricular septum thickness, diastolic left ventricular posterior wall thickness, and systolic left ventricular posterior wall thickness are not increased

congestive heart failure ( J:117386 )

• mice develop progressive congestive heart failure

behavior/neurological

decreased food intake ( J:117386 )

• mice show a 51% reduction in food intake

decreased locomotor activity ( J:117386 )

• mice hardly run on a running wheel apparatus when it is placed in their cage

• mice administered MnTBAP show improvement in physical activity

fatigue ( J:117386 )

• mice develop signs of fatigue as early as 8 weeks of age when mice begin to die

cellular

cardiac interstitial fibrosis ( J:117386 )

• diffuse fibrotic scars surround myocardial cells

• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles

abnormal mitochondrial crista morphology ( J:117386 )

• cristae of mitochondria in the heart left ventricular wall are rough, irregular, abnormally wound, and concentrated in the central zone of the matrix

• however, no abnormal crystals or droplets in mitochondria are seen

decreased mitochondrial size ( J:117386 )

• heart left ventricular wall shows small mitochondria

abnormal oxidative phosphorylation ( J:117386 )

• mice show suppressed oxidative phosphorylation in myocardium with heart mitochondria generating less ATP

abnormal mitochondrial ATP synthesis coupled electron transport ( J:117386 )

• activity of Complex II is hardly detected in cardiac muscle and no enzymatic activity of Complex II is seen in skeletal muscle

• NADH-cytochrome c reductase activity in the heart and skeletal muscle is inhibited and succinate-cytochrome c reductase activity is reduced even more

oxidative stress ( J:117386 )

• mice exhibit enhanced reactive oxygen species (superoxide) generation with increased lipid peroxidation in heart and skeletal muscle mitochondria

• higher levels of malondialdehyde are detected in heart mitochondria, indicating oxidative damage in mitochondria

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

muscle

abnormal cardiac muscle tissue morphology ( J:117386 )

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

abnormal myocardium layer morphology ( J:117386 )

• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei

myocardial fiber degeneration ( J:117386 )

• left ventricular wall shows myocardial degeneration

• however, apoptotic cell death is not seen in myocardium or skeletal muscle

cardiac muscle necrosis ( J:117386 )

• some of the fibrotic foci are due to necrotic changes of the myocardium

dilated cardiomyopathy ( J:117386 )

• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:117386 )

• cardiac contractility is depressed in 2 and 4 month old mice as assessed by fractional shortening and ejection fraction

• mice administered the antioxidant manganese 5, 10, 15, 20-tetrakis (4-benxoic acid) porphyrin (MnTBAP) exhibit improvement in cardiac function but no effect on heart weight

abnormal skeletal muscle morphology ( J:117386 )

• skeletal muscle of the tibialis anterior muscle shows similar but modest ultrastructural defects as in cardiac muscle

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:117386