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Phenotypes Associated with This Genotype
Genotype
MGI:5907992
Allelic
Composition
Sod2tm1Shs/Sod2tm1Shs
Tg(Ckmm-cre)5Khn/0
Genetic
Background
involves: C57BL/6CrSlc * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sod2tm1Shs mutation (0 available); any Sod2 mutation (18 available)
Tg(Ckmm-cre)5Khn mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• all mice show cardiac enlargement at 16 weeks of age
• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months
• mice show a 25% reduction in body weight at 16 weeks of age, without muscle atrophy
• mice begin to exhibit growth retardation at 8 weeks of age

cardiovascular system
• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls
• interstitial storage of excess glycogen in hearts at 15 weeks of age
• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei
• left ventricular wall shows myocardial degeneration
• however, apoptotic cell death is not seen in myocardium or skeletal muscle
• some of the fibrotic foci are due to necrotic changes of the myocardium
• all mice show cardiac enlargement at 16 weeks of age
• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months
• left ventricular wall shows small mitochondria associated with scattered abnormal vacuoles
• dilation of both left and right ventricles
• the left ventricular end-diastolic and end-systolic diameters are increased indicating left ventricular dilation
• diffuse fibrotic scars surround myocardial cells
• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles
• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy
• 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
• 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
• mice develop progressive congestive heart failure

behavior/neurological
• mice show a 51% reduction in food intake
• mice hardly run on a running wheel apparatus when it is placed in their cage
• mice administered MnTBAP show improvement in physical activity
• mice develop signs of fatigue as early as 8 weeks of age when mice begin to die

cellular
• some of the fibrotic foci are due to necrotic changes of the myocardium
• 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
• heart left ventricular wall shows small mitochondria
• mice show suppressed oxidative phosphorylation in myocardium with heart mitochondria generating less ATP
• 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
• 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
• interstitial storage of excess glycogen in hearts at 15 weeks of age

muscle
• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls
• interstitial storage of excess glycogen in hearts at 15 weeks of age
• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei
• left ventricular wall shows myocardial degeneration
• however, apoptotic cell death is not seen in myocardium or skeletal muscle
• some of the fibrotic foci are due to necrotic changes of the myocardium
• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy
• 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
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
01/24/2023
MGI 6.22
The Jackson Laboratory