OrganismMus musculus
Aging PhenotypeShortened life-span
Allele TypeRecessive
StrainCD1 (outbred) Also crossed with D2, B6, and others
DescriptionSod2 -/- mice are born smaller, pale and less vigorous, and they die within 7-10 days (Li et al, 1995). The major problems are dilated cardiomyopathy, accumulation of lipid in various tissues particularly liver and skeletal muscle, and metabolic acidosis (Li et al, 1995). In another group (and different strain background) Sod2-/- mice had severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive weakness, fatigue, and circling behavior (Lebovitz et al, 1996). Treatment of Sod2-/- mice with EUK-8, EUK-134, or EUK-189 superoxide dismutase/catalase mimetics partially rescues the short life-span (mean life-span 14-28 days) and other phenotypes (Melov et al., 1998).
Gene FunctionThe Sod2 gene encodes Mn-superoxide dismutase (MnSOD) located in the mitochondrial matrix. It protects against superoxide produced as a byproduct of oxidative phosphorylation.
Other PhenotypesThe mitochondrial ultrastructure is normal initially (Li et al, 1995). There is severe reduction in succinate dehydrogenase and aconitase activities, especially in the heart (Li et al, 1995). Older mice (more than 7 days old) show mitochondrial injury in degenerating neurons and cardiac myocytes (Lebovitz et al, 1996). Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3-methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage (Melov et al., 1999).
HomologsS.c. SOD2
S.p. Spac1486.01p, Spbc3h7.04
C.e. sod-2, sod-3
D.m. sod2
R.n. Sod2
H.s. SOD2
Primary ReferenceLi, Y., Huang, T. T., Carlson, E. J., Melov, S., Ursell, P. C., Olson, J. L., Noble, L. J., Yoshimura, M. P., Berger, C., Chan, P. H., and et al. (1995). Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. [Abstract]
Other ReferencesLebovitz, R. M., Zhang, H., Vogel, H., Cartwright, J., Jr., Dionne, L., Lu, N., Huang, S., and Matzuk, M. M. (1996). Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 9 [Abstract]
Melov, S., Schneider, J. A., Day, B. J., Hinerfeld, D., Coskun, P., Mirra, S. S., Crapo, J. D., and Wallace, D. C. (1998). A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase. Nat Genet 18, 159-63. [Abstract]
Melov, S., Coskun, P., Patel, M., Tuinstra, R., Cottrell, B., Jun, A. S., Zastawny, T. H., Dizdaroglu, M., Goodman, S. I., Huang, T. T., Miziorko, H., Epstein, C. J., and Wallace, D. C. (1999). Mitochondrial disease in superoxide dismutase 2 mutant mice. [Abstract]
Relevant LinksJAX:
Keywordsmouse, M. musculus, oxidative stress, mitochondria, neurons, metabolism