Strain Detail Sheet

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

Sod2^tm1Cje/Sod2⁺

        B6.Cg-Sod2<tm1Cje>/Mmmh

• mortality/aging
  • mortality/aging (MGI Ref ID J:87514)
    • no difference in life span or biochemical and physiological indices of aging are detected
• tumorigenesis
  • increased tumor incidence (MGI Ref ID J:87514)
    • more than 80% have neoplastic lesions by 26-28 months of age compared to 41% of wild-type mice; however the types and severity of lesions are similar to those in wild-type mice
    • the incidence of mice with multiple tumor types is increased to 66.6% compared to 18.5% in wild-type mice
    • increased lymphoma incidence (MGI Ref ID J:87514)
      • incidence is increased to 61% compared to 22% in wild-type mice
• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref ID J:108637)
    • aconitase and NADH-oxidoreductase (with CoQ as a substrate) activities are reduced by 35% and 45%, respectively, in hearts; however, mitochondrial fumerase and cytosolic aconitase and glutamine synthetase activities are not reduced
    • the speed of induction of permeability transition by calcium is significantly increased in heart mitochondria
    • abnormal aerobic energy metabolism (MGI Ref ID J:108637)
      • the respiratory control ratio for complex I and state 3 respiration (with glutamate and malate as substrates) are reduced by 37%; however, state 4 respiration is similar to controls
  • oxidative stress (MGI Ref IDs J:108637, J:87514)
    • increased cardiomyocyte apoptosis after treatment with t-BuOOH to induce oxidative stress compared to controls but less than in homozygous cells (MGI Ref ID J:108637)
    • significantly higher levels of oxidative DNA damage (measured as 8oxodG) are detected in mitochondrial and nuclear DNA at all ages examined (MGI Ref ID J:87514)
    • treatment with 50 mg paraquat / kg resulted in loss of 30% of heterozygotes within 4 days, unlike wild-type mice which all survived (MGI Ref ID J:87514)

Sod2^tm1Cje/Sod2^tm1Cje

        B6.Cg-Sod2<tm1Cje>/Mmmh

• mortality/aging
  • complete perinatal lethality (MGI Ref ID J:73998)
    • mean life span is 0.9 +/- 0.3 days
    • at E19 when delivered by cesarean section only 11.6% are homozygous and after natural birth only 8.4% are homozygous
    • mean life span is reduced compared to mice on a congenic DBA2/J or hybrid C57BL/6J and DBA2/J background
  • partial lethality throughout fetal growth and development (MGI Ref ID J:73998)
    • at E15, 4 of 19 fetuses are dead
• cardiovascular system phenotype
  • dilated cardiomyopathy (MGI Ref ID J:73998)
    • at E15, moderate to massive enlargement with the largest hearts having dilated left and right ventricular cavities with thinner muscular walls
    • dilated cardiomyopathy is seen on a congenic C57BL/6J background but not in mice on congenic DBA/2J or hybrid C57BL/6J and DBA/2J backgrounds
  • dilated heart left ventricle (MGI Ref ID J:73998)
    • dilated left and right ventricles are seen in severe cases
  • dilated heart right ventricle (MGI Ref ID J:73998)
    • dilated left and right ventricles are seen in severe cases
  • enlarged heart (MGI Ref ID J:73998)
    • at E15, moderate to massive enlargement is seen
  • thin ventricular wall (MGI Ref ID J:73998)
    • seen with dilated ventricles in severe cases
• growth/size phenotype
  • decreased fetal size (MGI Ref ID J:73998)
    • at E15, surviving mice are 21% smaller than age-matched wild-type littermates
• cellular phenotype
  • oxidative stress (MGI Ref ID J:108637)
    • increased cardiomyocyte apoptosis after treatment with t-BuOOH to induce oxidative stress
• muscle phenotype
  • dilated cardiomyopathy (MGI Ref ID J:73998)
    • at E15, moderate to massive enlargement with the largest hearts having dilated left and right ventricular cavities with thinner muscular walls
    • dilated cardiomyopathy is seen on a congenic C57BL/6J background but not in mice on congenic DBA/2J or hybrid C57BL/6J and DBA/2J backgrounds

Sod2^tm1Cje/Sod2^tm1Cje

        involves: C57BL/6J

• mortality/aging
  • complete postnatal lethality (MGI Ref ID J:45913)
    • die between 3 and 13 days of age
    • treatment with Manganese 5, 10 ,15, 20-tetrakis (4-benzoic acid) porpryrin (MnTBAP, a superoxide dismutase mimetic that does not cross the blood-brain barrier) increases survival time to a mean life span of 16.4 days compared to 8.3 days without treatment
• cardiovascular system phenotype
  • dilated cardiomyopathy (MGI Ref ID J:45913)
    • not detected in mice treated with MnTBAP
• nervous system phenotype
  • abnormal brainstem morphology (MGI Ref ID J:45913)
    • 9 of 16 mice older than 12 days of age display focal spongiform changes
    • vacuoles are most commonly seen in the reticulotegmental nucleus of the pons, the superior and medioventral periolivary nuclei, and in regions of the motor nucleus of cranial nerves V and VII
  • abnormal cerebellum morphology (MGI Ref ID J:45913)
    • 9 of 16 mice older than 12 days of age display focal spongiform changes
  • abnormal cerebral cortex morphology (MGI Ref ID J:45913)
    • mice older than 12 days of age display symmetric spongiform changes in large areas of the cerebral cortex, primarily in the mid to lower layers of the grey matter and the immediate subcortical white matter
    • vacuoles are mostly present in the neuropil and occasionally in the neuronal perikaryon
  • abnormal optic nerve morphology (MGI Ref ID J:71457)
    • cross-sectional area is smaller; however, the ultrastructure appears normal in 20 to 21 day old MnTBAP treated mice
  • brain vacuoles (MGI Ref ID J:45913)
    • no changes in brain morphology are seen in untreated mice before 10 days of age
    • many of the vacuoles are surrounded by thin myelin lamellae
  • spongiform encephalopathy (MGI Ref ID J:45913)
    • in MnTBAP treated mice
• behavior/neurological phenotype
  • abnormal gait (MGI Ref ID J:45913)
    • at about P12 MnTBAP treated mice develop ataxia in the hindlimbs with alternating extensor dystonic-like posturing of the hindlimbs and pivoting on the extended limb
  • ataxia (MGI Ref ID J:45913)
    • mice treated with MnTBAP develop progressive ataxia starting in the hindlimbs at about P12 and eventually spreading to the frontlimbs
    • older mice display a wide-based gait, sway from side to side, and frequently fall with falls sometimes resulting in multiple rolls
  • impaired righting response (MGI Ref ID J:45913)
    • in MnTBAP treated mice
  • tremors (MGI Ref ID J:45913)
    • in MnTBAP treated mice intermittent head tremors develop after P12
• vision/eye phenotype
  • abnormal optic nerve morphology (MGI Ref ID J:71457)
    • cross-sectional area is smaller; however, the ultrastructure appears normal in 20 to 21 day old MnTBAP treated mice
  • abnormal retina morphology (MGI Ref ID J:71457)
    • in 20 to 21 day old MnTBAP treated mice total retinal thickness, peripheral retinal thickness, and thickness of the combined nerve fiber, ganglion cell, and inner plexiform layers are reduced
    • unlike wild-type mice total retinal thickness does not increase between 9-10 and 20-21 days of age
    • abnormal retinal photoreceptor layer (MGI Ref ID J:71457)
      • the central and overall photoreceptor layer are thinner at 9-10 and 20-21 days of age, respectively, in MnTBAP treated mice
    • abnormal retinal pigment epithelium morphology (MGI Ref ID J:71457)
      • abnormal mitochondria are more common at 16 and 20-21 days of age in MnTBAP treated mice compared to controls
      • mitochondrial abnormalities include foci of swelling, matrix pallor, and disorganization of the cristae
    • thin retinal inner nuclear layer (MGI Ref ID J:71457)
      • thinner at 20-21 days of age in MnTBAP treated mice
• liver/biliary system phenotype
  • hepatic steatosis (MGI Ref ID J:45913)
    • ipid accumulation is decreased with MnTBAP treatment
• growth/size phenotype
  • postnatal growth retardation (MGI Ref ID J:45913)
    • weight gain is improved with MnTBAP treatment
• muscle phenotype
  • dilated cardiomyopathy (MGI Ref ID J:45913)
    • not detected in mice treated with MnTBAP
• pigmentation phenotype
  • abnormal retinal pigment epithelium morphology (MGI Ref ID J:71457)
    • abnormal mitochondria are more common at 16 and 20-21 days of age in MnTBAP treated mice compared to controls
    • mitochondrial abnormalities include foci of swelling, matrix pallor, and disorganization of the cristae

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.

Sod2^tm1Cje/Sod2⁺

        D2.Cg-Sod2<tm1Cje>

• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref ID J:73998)
    • at P5 mithochondrial but not cytoplasmice aconitase activity is reduced in the brain, heart, lung, liver, kidney, and skeletal muscle
    • this reduction is not as severe as in homozygotes

Sod2^tm1Cje/Sod2⁺

        involves: C57BL/6J * CD-1

• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref ID J:67874)
    • liver mitochondria are more prone to permeability transition following calcium addition
    • liver mitochondrial membrane electrochemical potential is lower than in wild-type
    • liver mitochondrial oxidative phosphorylation complexes I, II, II + III, and IV and citrate synthase are elevated 25% - 75% in 20 to 25 month old mice
    • abnormal aerobic energy metabolism (MGI Ref ID J:67874)
      • state III respiratory rate is reduced in liver cells at 5 and 10 - 14 months of age, but by 20 - 25 months control rates decrease so that they are similar to homozygotes
      • state IV respiration rate is increased in 10 - 14 and 20 - 25 month old mice but not in young (5 month old) mice
      • state III respiratory control ratios are reduced in young and middle aged mice but closer to normal in old mice
  • oxidative stress (MGI Ref ID J:67874)
    • at 10 - 14 months of age, liver mitochondria contain twice as much lipid hydroperoxides as in controls, but lipid peroxide levels decrease in old homozygotes
• liver/biliary system phenotype
  • increased hepatocyte apoptosis (MGI Ref ID J:67874)
    • increased 3-fold at 20 - 25 months of age

Sod2^tm1Cje/Sod2⁺

        involves: C57BL/6J * DBA/2J

• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref ID J:73998)
    • at P5 mithochondrial but not cytoplasmice aconitase activity is reduced in the brain, heart, lung, liver, kidney, and skeletal muscle
    • this reduction is not as severe as in homozygotes

Sod2^tm1Cje/Sod2^tm1Cje

        D2.Cg-Sod2<tm1Cje>

• mortality/aging
  • complete postnatal lethality (MGI Ref ID J:73998)
    • mean life span is 8.7 +/- 0.3 days
    • mean life span is longer than on a congenic C57BL/6J background but shorter than on a hybrid C57BL/6J DBA/2J background
• cardiovascular system phenotype
  • cardiac hypertrophy (MGI Ref ID J:73998)
    • mild
  • increased heart weight (MGI Ref ID J:73998)
    • heart weight to body weight ratios are progressively increased with age and show mild hypertrophy but no myocardial inflammation or fibrosis
    • no dilated cardiomyopathy is seen unlike mice on a congenic C57BL/6J or CD-1 background
• homeostasis/metabolism phenotype
  • abnormal blood gas level (MGI Ref ID J:73998)
    • increase in pO2 and decrease in pCO2 suggest a compensatory increase in respiration as a result of metabolic acidosis
    • changes in pO2 and pCO2 are smaller than in mice on a hybrid C57BL/6J DBA/2J background
  • abnormal blood homeostasis (MGI Ref ID J:73998)
    • acidosis (MGI Ref ID J:73998)
      • severe metabolic acidosis
      • by P5 a rapid decline in HCO3 levels and blood pH is seen
    • decreased circulating glucose level (MGI Ref ID J:73998)
      • seen earlier in congenic mice than in mice on a hybrid C57BL/6J and DBA/2J background
    • increased blood urea nitrogen level (MGI Ref ID J:73998)
      • seen earlier in congenic mice than in mice on a hybrid C57BL/6J and DBA/2J background
    • increased circulating alkaline phosphatase level (MGI Ref ID J:73998)
      • seen in some older mice
    • increased circulating aspartate transaminase level (MGI Ref ID J:73998)
      • seen in some older mice
    • increased circulating ketone body level (MGI Ref ID J:73998)
      • higher levels and seen earlier than in homozygotes on a hybrid C57BL/6J and DBA/2J background
  • abnormal enzyme/ coenzyme level (MGI Ref ID J:73998)
    • at P5, heart levels of SOD1 activit y are increased unlike mice on a hybrid C57BL/6J DBA/2J background where SOD1 activity is also increased in the brain, liver, and lung
    • increased circulating alkaline phosphatase level (MGI Ref ID J:73998)
      • seen in some older mice
    • increased circulating aspartate transaminase level (MGI Ref ID J:73998)
      • seen in some older mice
  • abnormal urine homeostasis (MGI Ref ID J:73998)
    • at P5 urinary organic acid levels are elevated
  • hyperoxia (MGI Ref ID J:73998)
    • a 20% increase in pO2 is seen
    • increase is smaller than in mice on a hybrid C57BL/6J and DBA/2J background
  • hypocapnia (MGI Ref ID J:73998)
    • a 24% decrease in pCO2 is seen
    • decrease is smaller than in mice on a hybrid C57BL/6J and DBA/2J background
• liver/biliary system phenotype
  • hepatic steatosis (MGI Ref ID J:73998)
    • large amounts of fat in the liver compared to wild-type or homozygotes on a hybrid C57BL/6J and DBA/2J background
• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref ID J:73998)
    • mithochondrial but not cytoplasmice aconitase activity is reduced in the brain, heart, lung, liver, kidney, and skeletal muscle
• renal/urinary system phenotype
  • abnormal urine homeostasis (MGI Ref ID J:73998)
    • at P5 urinary organic acid levels are elevated
• growth/size phenotype
  • decreased body weight (MGI Ref ID J:73998)

Sod2^tm1Cje/Sod2^tm1Cje

        involves: C57BL/6J * CD-1

• mortality/aging
  • complete postnatal lethality (MGI Ref ID J:29899)
    • by 4 - 5 days after birth, 37.5% are dead and almost all die by 10 days of age
• cellular phenotype
  • abnormal cell physiology (MGI Ref ID J:52592)
    • an increase in oxidative DNA lesions is seen in cells from the heart and brain, but not in liver cells
    • abnormal mitochondrial physiology (MGI Ref ID J:52592)
      • at 4 to 6 days of age, succinate dehydrogenase (complex II + III) activity is reduced to 35% and 24% of control in mitochondria from skeletal muscle and heart, respectively
      • at 4 to 6 days of age, complex I and citrate synthase activity are reduced to 59% and 32% of control in heart
      • at 9 to 10 days of age aconitase activity is reduced by 89% and 67-76% in the heart and various regions of the brain, respectively
      • liver mitochondria show a 36% decrease in 3-hydroxy-3-methylglutaryl-CoA lyase activity
    • abnormal mitochondrial physiology (MGI Ref ID J:29899)
      • aconitase activity is reduced by about 43%, 37%, and 22% in the heart, liver, and brain, respectively; however at P4 - 5 mitochondrial morphology appears normal
• cardiovascular system phenotype
  • cardiac fibrosis (MGI Ref ID J:29899)
    • endocardial fibrosis
  • cardiac hypertrophy (MGI Ref ID J:29899)
    • ventricular
  • dilated cardiomyopathy (MGI Ref ID J:29899)
    • enlarged hearts with a dilated left ventricular, reduced left ventricular wall thickness, hypertrophy and endocardial fibrosis but no signs of heart failure are seen
• liver/biliary system phenotype
  • abnormal liver physiology (MGI Ref ID J:29899)
    • slightly decreased glutamate oxaloacetate transaminase levels but normal glutamate pyruvate transaminase and bilirubin levels
  • hepatic steatosis (MGI Ref ID J:29899)
  • increased liver weight (MGI Ref ID J:29899)
    • weight is increased relative to body weight
• behavior/neurological phenotype
  • fatigue (MGI Ref ID J:29899)
    • fatigue rapidly after any exertion
• homeostasis/metabolism phenotype
  • abnormal blood homeostasis (MGI Ref ID J:29899)
    • lower serum lactate concentration
    • acidosis (MGI Ref ID J:29899)
      • compensated metabolic acidosis
    • increased circulating ketone body level (MGI Ref ID J:29899)
  • abnormal urine homeostasis (MGI Ref ID J:52592)
    • at 9, 10, 14 and 15 days of age increased concentrations of organic acids are found in the urine
  • decreased body surface temperature (MGI Ref ID J:29899)
    • neonates have surface temperatures that are 2.6 degrees C lower than controls
• hematopoietic system phe notype
  • decreased hematocrit (MGI Ref ID J:29899)
    • seen in neonates
• muscle phenotype
  • abnormal skeletal muscle morphology (MGI Ref ID J:29899)
    • lipid deposits
  • dilated cardiomyopathy (MGI Ref ID J:29899)
    • enlarged hearts with a dilated left ventricular, reduced left ventricular wall thickness, hypertrophy and endocardial fibrosis but no signs of heart failure are seen
  • hypotonia (MGI Ref ID J:29899)
    • seen in neonates
• growth/size phenotype
  • postnatal growth retardation (MGI Ref ID J:29899)
    • mice that survive to 4 - 5 days of age are severely growth retarded
• other phenotype
  • calcinosis (MGI Ref ID J:29899)
    • calcification of the submucosal regions of the small intestine
• renal/urinary system phenotype
  • abnormal urine homeostasis (MGI Ref ID J:52592)
    • at 9, 10, 14 and 15 days of age increased concentrations of organic acids are found in the urine
• integument phenotype
  • pallor (MGI Ref ID J:29899)

Sod2^tm1Cje/Sod2^tm1Cje

        involves: C57BL/6J * DBA/2J

• mortality/aging
  • complete postnatal lethality (MGI Ref ID J:73998)
    • mean life span is 15.7 +/- 0.5 days
    • mean life span is longer than on a congenic C57BL/6J or DBA/2J background
• cardiovascular system phenotype
  • cardiac hypertrophy (MGI Ref ID J:73998)
    • mild
  • increased heart weight (MGI Ref ID J:73998)
    • heart weight to body weight ratios are progressively increased with age and show mild hypertrophy but no myocardial inflammation or fibrosis
    • no dilated cardiomyopathy is seen unlike mice on a congenic C57BL/6J or CD-1 background
• homeostasis/metabolism phenotype
  • abnormal blood gas level (MGI Ref ID J:73998)
    • changes in pO2 and pCO2 are larger than in mice on a congenic DBA/2J background
  • abnormal blood homeostasis (MGI Ref ID J:73998)
    • abnormal blood pH regulation (MGI Ref ID J:73998)
      • a steady mild decline in HCO3 levels is seen resulting in maintenance of blood pH in the normal range through P15, unlike the rapid decline seen in mice on a congenic DBA2/J background
      • acidosis (MGI Ref ID J:73998)
        • milder than in mice on a congenic DBA/2J background
    • decreased circulating glucose level (MGI Ref ID J:73998)
      • seen later in hybrid mice than in mice on a congenic DBA/2J background
    • increased blood urea nitrogen level (MGI Ref ID J:73998)
      • seen later in hybrid mice than in mice on a congenic DBA/2J background
    • increased circulating ketone body level (MGI Ref ID J:73998)
      • lower than in homozygotes on a congenic DBA/2J background
  • abnormal enzyme/ coenzyme level (MGI Ref ID J:73998)
    • at P5, brain, heart, lung, and liver levels of SOD1 activity are increased unlike mice on a congenic DBA/2J background where SOD1 activity is increased only in the heart
  • abnormal urine homeostasis (MGI Ref ID J:73998)
    • at P10 and P15 urinary organic acid levels are elevated but no evidence of lactic acidosis is seen at P15
  • hyperoxia (MGI Ref ID J:73998)
    • a 55% increase in pO2 is seen
    • increase is larger than in mice on a congenic DBA/2J background
  • hypocapnia (MGI Ref ID J:73998)
    • a 40% decrease in pCO2 is seen
    • decrease is larger than in mice on a congenic DBA/2J background
• liver/biliary system phenotype
  • liver/biliary system phenotype (MGI Ref ID J:73998)
    • do not accumulate large amounts of lipid in the liver unlike mice on a congenic DBA/2J background
• cellular phenotype
  • abnormal mitochondrial physiology (MGI Ref IDs J:98007, J:73998)
    • mitochondrial but not cytoplasmic aconitase activity is reduced in the brain, heart, lung, liver, kidney, and skeletal muscle (MGI Ref ID J:73998)
    • mitochondrial aconitase activities are reduced by 72%, 61%,60%, and 62% in the cortex, thalamus, hippocampus, and brainstem, respectively (MGI Ref ID J:98007)
• behavior/neurological phenotype
  • abnormal gait (MGI Ref ID J:98007)
    • tendency to push or walk backward
  • ataxia (MGI Ref ID J:98007)
    • at P11 unsteady movement are seen progressing rapidly to truncal instability
  • ataxia (MGI Ref ID J:73998)
    • progressive ataxia with age
  • seizures (MGI Ref IDs J:98007, J:73998)
    • frequent seizures are seen in older mice (MGI Ref ID J:73998)
    • by P14, frequent spontaneous seizures are seen (MGI Ref ID J:98007)
  • tremors (MGI Ref ID J:98007)
    • visible tremors at P11
• renal/urinary system phenotype
  • abnormal urine homeostasis (MGI Ref ID J:73998)
    • at P10 and P15 urinary organic acid levels are elevated but no evidence of lactic acidosis is seen at P15
• nervous system phenotype
  • abnormal brain morphology (MGI Ref ID J:98007)
    • abnormal brainstem morphology (MGI Ref ID J:98007)
      • vacuolar degeneration is seen in discrete regions
      • abnormal trigeminal V mesencephalic nucleus morphology (MGI Ref ID J:98007)
        • degenerative changes are detected by P11-13
      • abnormal trigeminal motor nucleus morphology (MGI Ref ID J:98007)
        • degenerative changes are detected by P11-13
    • abnormal forebrain morphology (MGI Ref ID J:98007)
      • abnormal frontal lobe morphology (MGI Ref ID J:98007)
        • vacuolar degeneration is seen in deep layers of the motor cortex by P11-13
      • abnormal hippocampus morphology (MGI Ref ID J:98007)
        • vacuolar degeneration is seen in discrete regions
      • abnormal thalamus morphology (MGI Ref ID J:98007)
        • vacuolar degeneration is seen in discrete regions
  • axon degeneration (MGI Ref ID J:98007)
    • in regions of vacuolar degeneration, enlarged and degenerating mitochondria are found in the neurons and axons and the thickness of the myelin sheaths are reduced
  • neuron degeneration (MGI Ref ID J:98007)
    • in regions of vacuolar degeneration, enlarged and degenerating mitochondria are found in the neurons and axons and the thickness of the myelin sheaths are reduced
    • degeneration is first seen around P11-13 and becomes more extensive by P15
  • seizures (MGI Ref IDs J:98007, J:73998)
    • frequent seizures are seen in older mice (MGI Ref ID J:73998)
    • by P14, frequent spontaneous seizures are seen (MGI Ref ID J:98007)
• muscle phenotype
  • abnormal skeletal muscle fiber morphology (MGI Ref ID J:98007)
    • proliferation of mitochondria located in clusters near the sarcolemmal membrane
    • decreased skeletal muscle fiber size (MGI Ref ID J:98007)
• growth/size phenotype
  • decreased body weight (MGI Ref ID J:73998)