Li 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, Wallace D C, Epstein C J
Department of Neurosurgery, University of California, San Francisco 94143-0748, USA.
Nat Genet. 1995 Dec;11(4):376-81. doi: 10.1038/ng1295-376.
The Sod2 gene for Mn-superoxide dismutase (MnSOD), an intramitochondrial free radical scavenging enzyme that is the first line of defense against superoxide produced as a byproduct of oxidative phosphorylation, was inactivated by homologous recombination. Homozygous mutant mice die within the first 10 days of life with a dilated cardiomyopathy, accumulation of lipid in liver and skeletal muscle, and metabolic acidosis. Cytochemical analysis revealed a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs. These findings indicate that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.
锰超氧化物歧化酶（MnSOD）的Sod2基因通过同源重组被灭活，MnSOD是一种线粒体内自由基清除酶，是对抗氧化磷酸化副产物超氧化物的第一道防线。纯合突变小鼠在出生后的前10天内死亡，伴有扩张型心肌病、肝脏和骨骼肌脂质蓄积以及代谢性酸中毒。细胞化学分析显示，心脏中的琥珀酸脱氢酶（复合体II）和乌头酸酶（一种三羧酸循环酶）活性严重降低，其他器官的降低程度较小。这些发现表明，MnSOD通过维持易被超氧化物直接灭活的线粒体酶的完整性，对组织的正常生物学功能是必需的。
