Phenotypes associated with this allele

• Allele Symbol: Sod2⁺
• Allele Name: wild type
• Allele ID: MGI:2431968
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Sod2^tm1Leb/Sod2^+	B6.129S7-Sod2^tm1Leb/J	MGI:3580498
ht2	Sod2^tm1Cje/Sod2^+	B6.Cg-Sod2^tm1Cje/Mmmh	MGI:3639892
ht3	Sod2^tm1Cje/Sod2^+	D2.Cg-Sod2^tm1Cje	MGI:3655210
ht4	Sod2^tm1.1Kskk/Sod2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3580873
ht5	Sod2^tm1(tetO-Sod2)Evbo/Sod2^+	involves: 129S4/SvJae * C57BL/6	MGI:4818491
ht6	Sod2^tm1Cje/Sod2^+	involves: C57BL/6J * CD-1	MGI:3639894
ht7	Sod2^tm1Cje/Sod2^+	involves: C57BL/6J * DBA/2J	MGI:3655225
cn8	Sod2^tm1Shs/Sod2^+ Tg(Cdh16-cre)91Igr/0	involves: C57BL/6 * C57BL/6CrSlc	MGI:5432218
cx9	Sod2^tm1Cje/Sod2^+ Tg(SOD1*G93A)1Gur/0	involves: C57BL/6 * CD-1 * SJL	MGI:4831000

Genotype
MGI:3580498

ht1

• Allelic Composition: Sod2^tm1Leb/Sod2⁺
• Genetic Background: B6.129S7-Sod2^tm1Leb/J

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

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:119972 )

N • aging heterozygotes exhibit no significant increase in the amount of age-related hearing loss relative to C57BL/6 control mice, with many animals over the age of 20 months being deaf or displaying ABR thresholds >80 dB SPL

N • contrary to expectation, ABR thresholds are only 12 dB higher in heterozygotes relative to C57BL/6 control mice (at various age groups including 6-9, 12, 15, 18-21 and 24 months and stimuli including click, 8, 16 and 32 kHz); no explanation for the relatively good hearing of three 24-month-old heterozygotes is provided

Genotype
MGI:3639892

ht2

• Allelic Composition: Sod2^tm1Cje/Sod2⁺
• Genetic Background: B6.Cg-Sod2^tm1Cje/Mmmh

mortality/aging

mortality/aging ( J:87514 )

N • no difference in life span or biochemical and physiological indices of aging are detected

neoplasm

increased tumor incidence ( 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 ( J:87514 )

• incidence is increased to 61% compared to 22% in wild-type mice

cellular

abnormal mitochondrial physiology ( 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 respiratory electron transport chain ( 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 ( J:87514 , J:108637 )

• significantly higher levels of oxidative DNA damage (measured as 8oxodG) are detected in mitochondrial and nuclear DNA at all ages examined (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 (J:87514)

• increased cardiomyocyte apoptosis after treatment with t-BuOOH to induce oxidative stress compared to controls but less than in homozygous cells (J:108637)

Genotype
MGI:3655210

ht3

• Allelic Composition: Sod2^tm1Cje/Sod2⁺
• Genetic Background: D2.Cg-Sod2^tm1Cje

cellular

abnormal mitochondrial physiology ( 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

Genotype
MGI:3580873

ht4

• Allelic Composition: Sod2^tm1.1Kskk/Sod2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cardiovascular system

abnormal myocardial fiber morphology ( J:98289 )

• accumulation of lipid droplets and mitochondrial clustering is seen in heterozygous hearts at 10 days of age

• swelling and disruption of mitochondrial membranes was seen in 7 out of 10 hearts at 10 days of age

cellular

increased cardiomyocyte apoptosis ( J:98289 )

• at 6 and to a greater extent at 10 days after birth signs of apoptosis were detected in cardiomyocytes and endocardial cells

oxidative stress ( J:98289 )

• increased formation of nitrotyrosine is seen in the myocardium of 3 and 10 day old heterozygotes

• clusters of cardiomyocytes show signs of lipid peroxidation in 7 out of 10 heterozygotes at 10 days of age

muscle

abnormal myocardial fiber morphology ( J:98289 )

• accumulation of lipid droplets and mitochondrial clustering is seen in heterozygous hearts at 10 days of age

• swelling and disruption of mitochondrial membranes was seen in 7 out of 10 hearts at 10 days of age

increased cardiomyocyte apoptosis ( J:98289 )

• at 6 and to a greater extent at 10 days after birth signs of apoptosis were detected in cardiomyocytes and endocardial cells

Genotype
MGI:4818491

ht5

• Allelic Composition: Sod2^{tm1(tetO-Sod2)Evbo}/Sod2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

cardiovascular system

increased myocardial fiber size ( J:162190 )

myocardium necrosis ( J:162190 )

abnormal heart left ventricle morphology ( J:162190 )

• mice exhibit increased left ventricular internal diameter in systole compared with wild-type mice

cardiac fibrosis ( J:162190 )

decreased heart left ventricle muscle contractility ( J:162190 )

• left ventricular fractional area change, ejection fraction, and fractional shortening are decreased compared to in wild-type mice

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:162190 )

• mice are more susceptible to doxorubicin treatment with increased myocardial apoptosis, senescence, and degeneration compared with wild-type mice

muscle

increased myocardial fiber size ( J:162190 )

myocardium necrosis ( J:162190 )

decreased heart left ventricle muscle contractility ( J:162190 )

• left ventricular fractional area change, ejection fraction, and fractional shortening are decreased compared to in wild-type mice

increased cardiomyocyte apoptosis ( J:162190 )

• mice are more susceptible to doxorubicin treatment with increased myocardial apoptosis, senescence, and degeneration compared with wild-type mice

cellular

increased cardiomyocyte apoptosis ( J:162190 )

• mice are more susceptible to doxorubicin treatment with increased myocardial apoptosis, senescence, and degeneration compared with wild-type mice

Genotype
MGI:3639894

ht6

• Allelic Composition: Sod2^tm1Cje/Sod2⁺
• Genetic Background: involves: C57BL/6J * CD-1

cellular

increased hepatocyte apoptosis ( J:67874 )

• increased 3-fold at 20 - 25 months of age

abnormal mitochondrial physiology ( 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 respiratory electron transport chain ( 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 ( 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

increased hepatocyte apoptosis ( J:67874 )

• increased 3-fold at 20 - 25 months of age

Genotype
MGI:3655225

ht7

• Allelic Composition: Sod2^tm1Cje/Sod2⁺
• Genetic Background: involves: C57BL/6J * DBA/2J

cellular

abnormal tricarboxylic acid cycle ( J:73998 )

• at P5 mitochondrial but not cytoplasmic aconitase activity is reduced in the brain, heart, lung, liver, kidney, and skeletal muscle

• this reduction is not as severe as in homozygotes

Genotype
MGI:5432218

cn8

• Allelic Composition: Sod2^tm1Shs/Sod2⁺; Tg(Cdh16-cre)91Igr/0
• Genetic Background: involves: C57BL/6 * C57BL/6CrSlc

renal/urinary system

abnormal renal tubule epithelium morphology ( J:174099 )

• mice show prominent epithelial cell swelling in the dilated distal tubules

cellular

oxidative stress ( J:174099 )

• mice display a significant increase in oxidative stress (tyrosine nitration) in dilated renal tubules

Genotype
MGI:4831000

cx9

• Allelic Composition: Sod2^tm1Cje/Sod2⁺; Tg(SOD1*G93A)1Gur/0
• Genetic Background: involves: C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:62381 )

• accelerated disease progression

• shorter lifespans than Tg(SOD1*G93A)1Gur mice

• mean decrease in survival is 11 days

behavior/neurological

impaired coordination ( J:62381 )

• worse motor performance in rotorod test than Tg(SOD1*G93A)1Gur mice starting from 106 days of age

nervous system

decreased substantia nigra size ( J:62381 )

• decreased number of total neurons within the substatia nigra at 110 days of age

abnormal motor neuron morphology ( J:62381 )

• microvesiculation within large ventral horn motor neurons at 90 days of age

decreased neuron number ( J:62381 )

• accelerated disease progression

• decreased number of total neurons within the ventral horns of the lumbar cord at 90 days of age

• greater neuronal loss than that in Tg(SOD1*G93A)1Gur mice at 110 days of age

decreased spinal cord ventral horn cell number ( J:62381 )

• decreased number of total neurons within the ventral horns of the lumbar cord starting at 90 days of age

• greater neuronal loss than that in Tg(SOD1*G93A)1Gur mice at 110 days of age

decreased spinal cord size ( J:62381 )

• atrophy of the lumbar spinal cord starting at 90 days of age