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Allele Symbol Allele Name Allele ID |
Sod2tm1Shs targeted mutation 1, Takuji Shirasawa MGI:2447406 |
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| Summary |
7 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 |
| 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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• 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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• some of the fibrotic foci are due to necrotic changes of the myocardium
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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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• 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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• 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
|
|
• some of the fibrotic foci are due to necrotic changes of the myocardium
|
|
• 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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• 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 04/16/2024 MGI 6.23 |
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