Analysis Tools|
Allele Symbol Allele Name Allele ID |
Sod2tm1Shs targeted mutation 1, Takuji Shirasawa MGI:2447406 |
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| Summary |
8 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutant mice exhibit normal liver histology relative to controls
• no increase in lipid peroxidation is observed following measurement of malondialdehyde (MDA) or 4-hydroxyalkenals (4-HAE) in mutant liver extracts, indicating absence of oxidative liver injury
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• although all mice reach adolescence, most or all die at ~4 months of age due to heart failure
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• at 4 months of age, hearts are significantly larger than in control mice
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• at 4 months of age, heart weight/body weight (HW/BW) ratio is significantly higher than in control mice
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• TEM analysis of 4-month-old LV myocardium shows damaged mitochondria with prominent disruption of the cristae, rupture of the double membrane, and vacuole formation
• mitochondria isolated from heart tissue show a significant increase in both absolute and percentile 4-HNE adducted proteins relative to control mitochondria
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• at 4 months of age, hearts are significantly larger than in control mice
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• at 4 months of age, heart weight/body weight (HW/BW) ratio is significantly higher than in control mice
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• at 4 months of age, left ventricular (LV) mass is significantly higher than in control mice
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• at 4 months of age, Massons trichome staining of LV heart tissue indicates cardiac fibrosis
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• at 4 months of age, electrophysiological studies show a significantly shorter ventricular effective refractory period (VERP) than in control mice
• however, no increase in the incidence of atrial fibrillation (AF) or atrial effective refractory periods (AERP) is observed
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• at 4 months of age, mice exhibit fatal dilated cardiomyopathy, characterized by decreased ejection fraction and fractional shortening along with increased LV internal diameter
• failing hearts show a marked increase in the expression of cardiomyocyte stress response genes Nppa and Nppb (encoding natriuretic peptides A and B, respectively)
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• isolated neonatal cardiomyocytes exhibit a significant decrease in the oxygen consumption rate (OCR) during basal conditions and after the addition of FCCP (an H+ ionophore/uncoupler) with no significant change in OCR after the addition of oligomycin (complex V inhibitor) or rotenone A + antimycin (complex I and III inhibitors, respectively); mitochondrial respiration, including spare respiratory capacity, ATP turnover, and maximum respiration, are significantly decreased relative to control cardiomyocytes
• moreover, neonatal cardiomyocytes show a drastic increase in both glycolysis and glycolytic reserve, as measured by an ECAR (extracellular acidification rate) assay, indicating a shift in energy metabolism from mitochondrial to glycolytic respiration
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• transthoracic M-mode echocardiography shows a significant increase in LV internal diameter during systole (LVID; s) and diastole (LVID; d) accompanied by systolic dysfunction, with a significant reduction in percentage fractional shortening (%FS) and percentage ejection fraction (%EF)
• moreover, mice show significantly increased LV volumes during systole (LV Vol; s) and diastole (LV Vol; d) as well as decreased intraventricular septum diameter during systole (IVS; s) and diastole (IVS; d), confirming dilated cardiomyopathy
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• at 4 months of age, mice show a significantly higher incidence of inducible ventricular tachycardia than control mice
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• at 4 months of age
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• TEM analysis of 4-month-old LV myocardium shows damaged mitochondria with prominent disruption of the cristae, rupture of the double membrane, and vacuole formation
• mitochondria isolated from heart tissue show a significant increase in both absolute and percentile 4-HNE adducted proteins relative to control mitochondria
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• mitochondria isolated from heart tissue show a ~2-fold reduction in the levels of cardiolipin, a phospholipid located exclusively in the inner mitochondrial membrane
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• TEM analysis of 4-month-old LV myocardium shows disorganization of mitochondrial cristae
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• mitochondria isolated from the myocardium of ~4-month-old mice exhibit a significant decrease in the oxygen consumption rate (OCR) during basal conditions and after the addition of FCCP, with no significant change in the OCR after the addition of oligomycin or antimycin A + rotenone; mitochondrial respiration, including spare respiratory capacity, ATP turnover, and maximum respiration, are significantly decreased relative to control mitochondria
• mitochondria isolated from the myocardium show a significant decrease in the activities of complex I (NADH dehydrogenase) and complex V (ATP synthase), without any major change in the activities of SDHA (succinate dehydrogenase complex flavoprotein subunit A; part of Complex II) or dihydrolipoamide dehydrogenase (DLD)
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• isolated cardiac mitochondria and neonatal cardiomyocytes show a shift in energy metabolism from OXPHOS to glycolysis
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• heart tissue and isolated cardiac mitochondria show a 3-fold increase in superoxide levels relative to those in control mice
• increase in reactive oxygen species (ROS) leads to subsequent overproduction of 4-HNE (a highly reactive, toxic aldehyde produced when ROS react with lipids such as cardiolipinin) inside mitochondria
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• TEM analysis of 4-month-old LV myocardium shows damaged mitochondria with prominent disruption of the cristae, rupture of the double membrane, and vacuole formation
• mitochondria isolated from heart tissue show a significant increase in both absolute and percentile 4-HNE adducted proteins relative to control mitochondria
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• at 4 months of age, mice exhibit fatal dilated cardiomyopathy, characterized by decreased ejection fraction and fractional shortening along with increased LV internal diameter
• failing hearts show a marked increase in the expression of cardiomyocyte stress response genes Nppa and Nppb (encoding natriuretic peptides A and B, respectively)
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• at 4 months of age, H&E staining of LV heart tissue shows sarcomere disruption, unlike in control hearts
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| N |
• despite a drastic reduction in cardiac SOD2 activity, mice show no major change in the activity of SOD1 (superoxide dismutase 1), catalase, or glutathione peroxidase in heart tissue
• moreover, GSH (reduced glutathione), GSSG (oxidized glutathione) and the GSH/GSSG ratio are not significantly altered in heart tissue
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• gastrocnemius and soleus muscle mass are not different from wild type
• no differences in muscle fiber morphology or in number of centrally located myofiber nuclei in gastrocnemius muscle compared to wild type
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• lipid oxidative damage is elevated in TA muscles of young mice
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• mitochondria isolated from glycolytic skeletal muscle of young mice release greater than two-fold more superoxide than those from glycolytic muscle of wild type controls
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• lactate levels differ from wild type significantly after 40 minutes of running
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• blood glucose levels are not significantly different up to 40 minutes of running but mutant mice utilize glucose at a fourfold faster rate than wild type from 40 minutes of running until exhaustion
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• aconitase activity in homogenates of glycolytic skeletal muscle is reduced by 56% and 52% in young male and female mice compared to wild type
• whereas levels in soleus muscle is not different from controls
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• glycolytic muscle function and running capacity are reduced in young mice compared to wild type
• maximum contractile force production in glycolytic and oxidative muscle is not different from wild type, while a significant decline in force during repeated contractions of the extensor digitorum longus or gastrocnemius is observed beyond that measured in wild type mice
• average minimum force produced by gastrocnemius muscle is 10% less than that in wild type, but that produced by the soleus muscle is not different from wild type
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| N |
• body mass in young female (5- to 8-month old) and male (3- to 4-month old) mice are not different from wild type; lean body mass is not different from wild type
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• mitochondria isolated from glycolytic skeletal muscle of young mice release greater than two-fold more superoxide than those from glycolytic muscle of wild type controls
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• blood glucose levels are not significantly different up to 40 minutes of running but mutant mice utilize glucose at a fourfold faster rate than wild type from 40 minutes of running until exhaustion
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• rate of peroxide (H2O2) production is reduced by about 33% with complex II-linked substrate (succinate+rotenone) but increased (by 56%) in the presence of a complex III inhibitor
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| N |
• no differences in body fat are detected compared with wild type
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| N |
• blood lactate and glucose fasting levels and nonfasted levels before exercise are not different from wild type
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• distance run on the treadmill is 55% less than the distance run by wild type
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• average time of exhaustion in treadmill running is about 63 minutes compared to about 139 minutes in wild type animals
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• the manganese-superoxide dismutase (Mn-SOD) intensity/fiber type area in type IIB muscle fibers is reduced by 70% relative to wild type
• aconitase protein in homogenates of glycolytic skeletal muscle from young female mice is reduced by 50%, whereas levels in soleus muscle is not different from controls
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• aconitase activity in homogenates of glycolytic skeletal muscle is reduced by 56% and 52% in young male and female mice compared to wild type
• whereas levels in soleus muscle is not different from controls
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• distance run on the treadmill is 55% less than the distance run by wild type
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• average time of exhaustion in treadmill running is about 63 minutes compared to about 139 minutes in wild type animals
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show prominent epithelial cell swelling in the dilated distal tubules
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• mice display a significant increase in oxidative stress (tyrosine nitration) in dilated renal tubules
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit no overt survival difference up to ~22 months of age relative to controls
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• at 8 weeks of age, mice exhibit a significantly smaller body weight relative to controls
• however, no significant differences in the weight of vital organs (kidney, liver, heart and lungs) are observed
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| N |
• mice exhibit no overt decrease in renal function, as measured by serum creatinine levels
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• mice show prominent epithelial cell swelling in the dilated distal tubules
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• mice exhibit dilated distal tubules within the cortex region relative to controls
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• dilated distal tubules show a significant increase in proteinacious casts within the tubular lumen
• acellular casts within distal tubules, collecting ducts, and Loops of Henle display positive staining for tyrosine nitration
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• mice display a significant increase in oxidative stress (tyrosine nitration) in dilated renal tubules
• tyrosine nitration is detected in cortical regions (dilated distal tubules and collecting ducts) as well as medullary regions (including the collecting ducts and Loops of Henle)
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| N |
• mice exhibit normal blood glucose levels relative to controls
• no significant difference in serum creatinine levels relative to controls
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| N |
• mice exhibit no significant change in systolic blood pressure relative to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no mutant mice are obtained after natural birth; however, when delivered by C-section mutants are found to be viable, anatomically normal and of normal size at E18, suggesting that death occurs at an early neonatal stage
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• all mice show cardiac enlargement at 16 weeks of age
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• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months
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• mice show a 25% reduction in body weight at 16 weeks of age, without muscle atrophy
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• mice begin to exhibit growth retardation at 8 weeks of age
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• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls
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• interstitial storage of excess glycogen in hearts at 15 weeks of age
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• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei
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• left ventricular wall shows myocardial degeneration
• however, apoptotic cell death is not seen in myocardium or skeletal muscle
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• some of the fibrotic foci are due to necrotic changes of the myocardium
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• all mice show cardiac enlargement at 16 weeks of age
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• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months
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• left ventricular wall shows small mitochondria associated with scattered abnormal vacuoles
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• dilation of both left and right ventricles
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• the left ventricular end-diastolic and end-systolic diameters are increased indicating left ventricular dilation
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• diffuse fibrotic scars surround myocardial cells
• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles
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• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy
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• 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
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• 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
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• mice develop progressive congestive heart failure
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• mice show a 51% reduction in food intake
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• mice hardly run on a running wheel apparatus when it is placed in their cage
• mice administered MnTBAP show improvement in physical activity
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• mice develop signs of fatigue as early as 8 weeks of age when mice begin to die
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• diffuse fibrotic scars surround myocardial cells
• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles
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• 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
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• heart left ventricular wall shows small mitochondria
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• 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
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• mice show suppressed oxidative phosphorylation in myocardium with heart mitochondria generating less ATP
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• 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
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• 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
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• interstitial storage of excess glycogen in hearts at 15 weeks of age
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• higher levels of malondialdehyde are detected in heart mitochondria, indicating oxidative damage in mitochondria
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• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls
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• interstitial storage of excess glycogen in hearts at 15 weeks of age
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• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei
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• left ventricular wall shows myocardial degeneration
• however, apoptotic cell death is not seen in myocardium or skeletal muscle
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• some of the fibrotic foci are due to necrotic changes of the myocardium
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• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy
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• 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
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• 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
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congestive heart failure | DOID:6000 | J:117386 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• left ventricle wall shows myocardial degeneration
• treatment with EUK-8, a superoxide dismutase and catalase mimetic, diminishes myocardial degeneration
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• left ventricle wall shows myocyte disarray
• EUK-8 treated mice show diminished myocyte disarray
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• progressively increasing heart-to-body weight ratio
• treatment with EUK-8, a superoxide dismutase and catalase mimetic, decreases heart weight
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• diffuse fibrotic scars surrounding myocardial cells
• EUK-8 treated mice show diminished fibrosis
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• heart dilatation
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• increase in left ventricular end-diastolic internal dimension (LVIDd)
• EUK-8 treatment for 4 weeks decreases LVIDd
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• increase in left ventricular end-diastolic internal dimension (LVIDd)
• EUK-8 treatment for 4 weeks decreases LVIDd
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• progressively increasing heart-to-body weight ratio
• treatment with EUK-8, a superoxide dismutase and catalase mimetic, decreases heart weight
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• diffuse fibrotic scars surrounding myocardial cells
• EUK-8 treated mice show diminished fibrosis
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• heart tissue exhibits oxidative DNA damage
• EUK-8 treatment attenuates oxidative DNA damage in heart tissue
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• telomerase activity is decreased in heart tissues, however telomere length is normal
• EUK-8 treatment restores normal telomerase activity
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• left ventricle wall shows myocardial degeneration
• treatment with EUK-8, a superoxide dismutase and catalase mimetic, diminishes myocardial degeneration
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• left ventricle wall shows myocyte disarray
• EUK-8 treated mice show diminished myocyte disarray
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congestive heart failure | DOID:6000 | J:171017 | ||
| dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:171017 | |
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 04/07/2026 MGI 6.24 |
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