Strain Name:

B6.129S7-Sod2tm1Leb/J

Stock Number:

002973

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Availability:

Repository- Live

Mice homozygous for Sod2tm1Leb die within 21 days after birth, and they exhibit several novel pathogenic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, progressive motor disturbances, and myocardial injury. These mice may be useful for studies of idiopathic cardiomyopathy and sporadic motor neuron disease.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x C57BL/6J (000664)         (Female x Male)   09-AUG-13
Mating SystemC57BL/6J (000664) x Heterozygote         (Female x Male)   09-AUG-13
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129S7 via AB2.1 ES cell line
Generation N5+20 (10-SEP-13)
Generation Definitions
 
Donating InvestigatorDr. Russell Lebovitz,   SUMA Partners

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Sod2tm1Leb targeted mutation die within 21 days after birth. They exhibit severe wasting and are clearly much smaller, weaker,and less coordinated than their wildtype and heterozygous littermates. Homoyzotes exhibit several novel pathogenic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, progressive motor disturbances, and myocardial injury.

Development
The Sod2tm1Leb targeted mutation was made by Dr. Russell Lebovitz. A 1.5 Kb HindIII fragment containing exons 1 and 2 of the Sod2 gene, as well as approximately 500bp immediately 5' of exon 1, was replaced with a human hypoxanthine phosphoribosyltransferase minigene driven by the phosphoglycerate kinase promoter. The transcription and translation start sites, the mitochondrial targeting sequence, and one of the three histidines that bind directly to the manganese cofactor, have been eliminated. The 129S7/SvEvBrd-Hprtb-m2-derived AB 2.1 ES cell line was used. The Sod2tm1Leb targeted mutation has been backcrossed more than 5 times to C57BL/6 mice.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Sod2tm1Leb allele
006883   B6.129S7-Ldlrtm1Her Sod2tm1Leb/J
View Strains carrying   Sod2tm1Leb     (1 strain)

Strains carrying other alleles of Sod2
024851   B6N.129S6-Sod2tm1(rtTA*M2,tetO)Jsg/J
View Strains carrying other alleles of Sod2     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Microvascular Complications of Diabetes, Susceptibility to, 6; MVCD6   (SOD2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Sod2tm1Leb/Sod2+

        B6.129S7-Sod2tm1Leb/J
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype
    • 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   (MGI Ref ID J:119972)
    • 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   (MGI Ref ID J:119972)

Sod2tm1Leb/Sod2tm1Leb

        B6.129S7-Sod2tm1Leb/J
  • mortality/aging
  • complete postnatal lethality
    • homozygotes survive for up to 3 weeks of age   (MGI Ref ID J:36148)
    • mutants with the slowest growth rates (4 of 8) usually die during the first postnatal week   (MGI Ref ID J:36148)
    • mutants with intermediate growth rates die within the second or third week   (MGI Ref ID J:36148)
  • growth/size/body phenotype
  • decreased body size
    • at P10, homozygotes are significantly smaller than wild-type littermates   (MGI Ref ID J:36148)
    • however, no skeletal abnormalities are observed and failure to thrive is unrelated to nursing difficulties   (MGI Ref ID J:36148)
    • decreased body length   (MGI Ref ID J:36148)
    • decreased body weight   (MGI Ref ID J:36148)
  • decreased total body fat amount
    • homozygotes display a significant reduction in adipose tissue mass   (MGI Ref ID J:36148)
  • postnatal growth retardation
    • reduction of postnatal growth rate is variable among mice, first evident between P2 and P7, and progressive until death by P18   (MGI Ref ID J:36148)
  • behavior/neurological phenotype
  • abnormal motor capabilities/coordination/movement
    • homozygotes display striking and progressive motor deficits   (MGI Ref ID J:36148)
    • circling   (MGI Ref ID J:36148)
    • weakness
      • homozygotes exhibit progressive limb weakness, as shown by impaired ability to hold onto a bar suspended above the cage for at least 5 sec without falling or scale a 60 degree incline   (MGI Ref ID J:36148)
  • fatigue
    • homozygotes display earlier onset of fatigue, as shown by reduced endurance only after 2-3 cycles of immersion into a small room-temperature water bath (vs 10 cycles in wild-type mice)   (MGI Ref ID J:36148)
  • hematopoietic system phenotype
  • anemia
    • homozygotes are severely anemic at the time of death   (MGI Ref ID J:36148)
  • decreased bone marrow cell number
    • homozygotes display a hypocellular bone marrow   (MGI Ref ID J:36148)
  • impaired myelopoiesis
    • within the bone marrow, all hematopoietic lineages appear to be reduced   (MGI Ref ID J:36148)
  • nervous system phenotype
  • neurodegeneration
    • homozygotes display degeneration of large CNS neurons, esp. in the basal ganglia and brainstem   (MGI Ref ID J:36148)
    • neurodegeneration is associated with extensive mitochondrial damage, loss of polysomes, clearing of the cytoplasm, a relative absence of rough ER, focal dilation of smooth ER, and ruffling of nuclear membranes   (MGI Ref ID J:36148)
    • in P10 basal ganglia, early cellular degeneration includes dispersion of cytoplasm, shedding of ribosomes, and balloning of mitochondria   (MGI Ref ID J:36148)
    • in affected brain and brainstem regions, occasional swollen neurites are observed; however, most structures and mitochondria remain intact   (MGI Ref ID J:36148)
  • cellular phenotype
  • abnormal mitochondrial physiology
    • at >P7, homozygotes show extensive mitochondrial injury in affected cardiac muscle cells and degenerating neurons   (MGI Ref ID J:36148)
  • adipose tissue phenotype
  • decreased total body fat amount
    • homozygotes display a significant reduction in adipose tissue mass   (MGI Ref ID J:36148)
  • muscle phenotype
  • decreased skeletal muscle mass
    • homozygotes display a significant reduction in skeletal muscle mass   (MGI Ref ID J:36148)
  • dilated cardiomyopathy
    • only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall   (MGI Ref ID J:36148)
    • affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions   (MGI Ref ID J:36148)
  • immune system phenotype
  • impaired myelopoiesis
    • within the bone marrow, all hematopoietic lineages appear to be reduced   (MGI Ref ID J:36148)
  • liver/biliary system phenotype
  • abnormal hepatocyte morphology
    • hepatic glycogen deposits appear coarsely granular and with a tendency towards centrilobular accumulation   (MGI Ref ID J:36148)
    • in addition, an abundance of intracellular lipid vacuoles is observed   (MGI Ref ID J:36148)
  • cardiovascular system phenotype
  • dilated cardiomyopathy
    • only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall   (MGI Ref ID J:36148)
    • affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions   (MGI Ref ID J:36148)
  • thin ventricular wall
    • homozygotes with extreme baloon-like cardiac dilatation (10%) display thinning of the ventricular wall   (MGI Ref ID J:36148)
  • homeostasis/metabolism phenotype
  • abnormal lipid homeostasis
    • homozygotes display an abundance of intracellular lipid vacuoles in hepatocytes   (MGI Ref ID J:36148)
    • homozygotes with extreme cardiac dilatation exhibit lipid peroxidation of mitochondrial membranes in affected myocytes   (MGI Ref ID J:36148)
    • homozygotes without extreme cardiac dilatation show increased accumulation of neutral lipid in myocytes but no mitochondrial injury   (MGI Ref ID J:36148)
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • ovaries from female homozygotes (4-10 days of age), transplanted to the bursa of wild-type hosts, display all stages of folliculogenesis including corpora lutea and give rise to viable offspring, suggesting normal ovarian function   (MGI Ref ID J:64299)
  • integument phenotype
  • pallor
    • homozygotes appear slightly pale   (MGI Ref ID J:36148)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Sod2tm1Leb related

Metabolism Research

Neurobiology Research
Metabolic Defects
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Sod2tm1Leb
Allele Name targeted mutation 1, Russell M Lebovitz
Allele Type Targeted (Null/Knockout)
Common Name(s) SOD2m1BCM; Sod2-; Sod2mlbcm;
Mutation Made ByDr. Russell Lebovitz,   SUMA Partners
Strain of Origin129S7/SvEvBrd-Hprt
ES Cell Line NameAB2.1
ES Cell Line Strain129S7/SvEvBrd-Hprt
Gene Symbol and Name Sod2, superoxide dismutase 2, mitochondrial
Chromosome 17
Gene Common Name(s) IPOB; MGC:6144; MNSOD; MVCD6; Sod-2; manganese SOD; manganese superoxide dismutase;
Molecular Note A human HPRT minigene driven by the PGK promoter replaced exons 1 and 2, and sequences approximately 500 bp immediately 5' of exon 1. The replaced region encodes the transcription and translation start sites, the mitochondrial targeting sequence, and oneof three histidines that bind directly to the manganese cofactor. Northern blot analysis of brain did not detect mRNA in homozygous mutant mice. Enzyme activity assays of heart did not detect active protein in homozygous mutant mice. [MGI Ref ID J:36148]

Genotyping

Genotyping Information

Genotyping Protocols

Human HPRT Melt Curve Analysis, Melt Curve Analysis
Human HPRT, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lebovitz RM; Zhang H; Vogel H; Cartwright J Jr; Dionne L; Lu N; Huang S; Matzuk MM. 1996. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 93(18):9782-7. [PubMed: 8790408]  [MGI Ref ID J:36148]

Additional References

Sod2tm1Leb related

Andrews ZB; Horvath TL. 2009. Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 296(4):E621-7. [PubMed: 19141680]  [MGI Ref ID J:148135]

Asimakis GK; Lick S; Patterson C. 2002. Postischemic recovery of contractile function is impaired in SOD2(+/-) but not SOD1(+/-) mouse hearts. Circulation 105(8):981-6. [PubMed: 11864929]  [MGI Ref ID J:103317]

Chrispell JD; Feathers KL; Kane MA; Kim CY; Brooks M; Khanna R; Kurth I; Hubner CA; Gal A; Mears AJ; Swaroop A; Napoli JL; Sparrow JR; Thompson DA. 2009. Rdh12 activity and effects on retinoid processing in the murine retina. J Biol Chem 284(32):21468-77. [PubMed: 19506076]  [MGI Ref ID J:153181]

Crane JD; Abadi A; Hettinga BP; Ogborn DI; MacNeil LG; Steinberg GR; Tarnopolsky MA. 2013. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle. PLoS One 8(12):e81879. [PubMed: 24324727]  [MGI Ref ID J:211014]

Das KC; Muniyappa H. 2013. Age-dependent mitochondrial energy dynamics in the mice heart: role of superoxide dismutase-2. Exp Gerontol 48(9):947-59. [PubMed: 23806974]  [MGI Ref ID J:210210]

Dugan LL; You YH; Ali SS; Diamond-Stanic M; Miyamoto S; DeCleves AE; Andreyev A; Quach T; Ly S; Shekhtman G; Nguyen W; Chepetan A; Le TP; Wang L; Xu M; Paik KP; Fogo A; Viollet B; Murphy A; Brosius F; Naviaux RK; Sharma K. 2013. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123(11):4888-99. [PubMed: 24135141]  [MGI Ref ID J:204683]

Esposito L; Raber J; Kekonius L; Yan F; Yu GQ; Bien-Ly N; Puolivali J; Scearce-Levie K; Masliah E; Mucke L. 2006. Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J Neurosci 26(19):5167-79. [PubMed: 16687508]  [MGI Ref ID J:108685]

Fan YY; Zhan Y; Aukema HM; Davidson LA; Zhou L; Callaway E; Tian Y; Weeks BR; Lupton JR; Toyokuni S; Chapkin RS. 2009. Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice. J Nutr 139(7):1328-32. [PubMed: 19458032]  [MGI Ref ID J:149998]

Hou Y; Ouyang X; Wan R; Cheng H; Mattson MP; Cheng A. 2012. Mitochondrial superoxide production negatively regulates neural progenitor proliferation and cerebral cortical development. Stem Cells 30(11):2535-47. [PubMed: 22949407]  [MGI Ref ID J:194645]

Huang TT; Carlson EJ; Raineri I; Gillespie AM; Kozy H; Epstein CJ. 1999. The use of transgenic and mutant mice to study oxygen free radical metabolism Ann N Y Acad Sci 893:95-112. [PubMed: 10672232]  [MGI Ref ID J:60488]

Jackson RM; Helton ES; Viera L; Ohman T. 1999. Survival, lung injury, and lung protein nitration in heterozygous MnSOD knockout mice in hyperoxia. Exp Lung Res 25(7):631-46. [PubMed: 10598322]  [MGI Ref ID J:103295]

Kashimshetty R; Desai VG; Kale VM; Lee T; Moland CL; Branham WS; New LS; Chan EC; Younis H; Boelsterli UA. 2009. Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 238(2):150-9. [PubMed: 19442681]  [MGI Ref ID J:151453]

Kinugawa S; Wang Z; Kaminski PM; Wolin MS; Edwards JG; Kaley G; Hintze TH. 2005. Limited exercise capacity in heterozygous manganese superoxide dismutase gene-knockout mice: roles of superoxide anion and nitric oxide. Circulation 111(12):1480-6. [PubMed: 15781740]  [MGI Ref ID J:108992]

Kirkland RA; Saavedra GM; Cummings BS; Franklin JL. 2010. Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases. J Neurosci 30(48):16114-27. [PubMed: 21123558]  [MGI Ref ID J:166748]

Le T; Keithley EM. 2007. Effects of antioxidants on the aging inner ear. Hear Res 226(1-2):194-202. [PubMed: 16843623]  [MGI Ref ID J:119972]

Lee YH; Chung MC; Lin Q; Boelsterli UA. 2008. Troglitazone-induced hepatic mitochondrial proteome expression dynamics in heterozygous Sod2(+/-) mice: two-stage oxidative injury. Toxicol Appl Pharmacol 231(1):43-51. [PubMed: 18495193]  [MGI Ref ID J:140073]

Liang LP; Patel M. 2004. Mitochondrial oxidative stress and increased seizure susceptibility in Sod2(-/+) mice. Free Radic Biol Med 36(5):542-54. [PubMed: 14980699]  [MGI Ref ID J:88798]

Matzuk MM; Dionne L; Guo Q; Kumar TR; Lebovitz RM. 1998. Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology 139(9):4008-11. [PubMed: 9724058]  [MGI Ref ID J:64299]

Muller FL; Lustgarten MS; Jang Y; Richardson A; Van Remmen H. 2007. Trends in oxidative aging theories. Free Radic Biol Med 43(4):477-503. [PubMed: 17640558]  [MGI Ref ID J:123504]

Ohashi M; Runge MS; Faraci FM; Heistad DD. 2006. MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 26(10):2331-6. [PubMed: 16873728]  [MGI Ref ID J:128050]

Ong MM; Latchoumycandane C; Boelsterli UA. 2007. Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicol Sci 97(1):205-13. [PubMed: 17150972]  [MGI Ref ID J:122231]

Ong MM; Wang AS; Leow KY; Khoo YM; Boelsterli UA. 2006. Nimesulide-induced hepatic mitochondrial injury in heterozygous Sod2(+/-) mice. Free Radic Biol Med 40(3):420-9. [PubMed: 16443156]  [MGI Ref ID J:105443]

Reddy VN; Kasahara E; Hiraoka M; Lin LR; Ho YS. 2004. Effects of variation in superoxide dismutases (SOD) on oxidative stress and apoptosis in lens epithelium. Exp Eye Res 79(6):859-68. [PubMed: 15642323]  [MGI Ref ID J:115465]

Roos CM; Hagler M; Zhang B; Oehler EA; Arghami A; Miller JD. 2013. Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice. Am J Physiol Heart Circ Physiol 305(10):H1428-39. [PubMed: 23997094]  [MGI Ref ID J:204531]

Srivastava S; Banerjee H; Chaudhry A; Khare A; Sarin A; George A; Bal V; Durdik JM; Rath S. 2007. Apoptosis-inducing factor regulates death in peripheral T cells. J Immunol 179(2):797-803. [PubMed: 17617569]  [MGI Ref ID J:149344]

Xiong Y; Shie FS; Zhang J; Lee CP; Ho YS. 2005. Prevention of mitochondrial dysfunction in post-traumatic mouse brain by superoxide dismutase. J Neurochem 95(3):732-44. [PubMed: 16248885]  [MGI Ref ID J:136792]

Yan C; Huang A; Wu Z; Kaminski PM; Wolin MS; Hintze TH; Kaley G; Sun D. 2005. Increased superoxide leads to decreased flow-induced dilation in resistance arteries of Mn-SOD-deficient mice. Am J Physiol Heart Circ Physiol 288(5):H2225-31. [PubMed: 15637112]  [MGI Ref ID J:98222]

Yang D; Elner SG; Lin LR; Reddy VN; Petty HR; Elner VM. 2009. Association of superoxide anions with retinal pigment epithelial cell apoptosis induced by mononuclear phagocytes. Invest Ophthalmol Vis Sci 50(10):4998-5005. [PubMed: 19458341]  [MGI Ref ID J:154540]

Yoshihara D; Fujiwara N; Ookawara T; Kato S; Sakiyama H; Yokoe S; Eguchi H; Suzuki K. 2009. Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice. Free Radic Biol Med 47(5):559-67. [PubMed: 19482077]  [MGI Ref ID J:151433]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryThis strain is maintained by mating C57BL/6J x heterozygote or heterozygote x C57BL/6J. Expected coat color from breeding: Black
Mating SystemHeterozygote x C57BL/6J (000664)         (Female x Male)   09-AUG-13
C57BL/6J (000664) x Heterozygote         (Female x Male)   09-AUG-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Sod2tm1Leb  
Price per Pair (US dollars $)Pair Genotype
$261.55C57BL/6J (000664) x Heterozygous for Sod2tm1Leb  
$260.05Heterozygous for Sod2tm1Leb x C57BL/6J (000664)  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Sod2tm1Leb  
Price per Pair (US dollars $)Pair Genotype
$340.10C57BL/6J (000664) x Heterozygous for Sod2tm1Leb  
$338.10Heterozygous for Sod2tm1Leb x C57BL/6J (000664)  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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