AN ADVERSE PROPERTY OF A FAMILIAL ALS-LINKED SOD1 MUTATION CAUSES MOTOR-NEURON DISEASE CHARACTERIZED BY VACUOLAR DEGENERATION OF MITOCHONDRIA
AN ADVERSE PROPERTY OF A FAMILIAL ALS-LINKED SOD1 MUTATION CAUSES MOTOR-NEURON DISEASE CHARACTERIZED BY VACUOLAR DEGENERATION OF MITOCHONDRIA
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DOI：
10.1016/0896-6273(95)90259-7
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发表时间：
1995-06-01
期刊：
影响因子：
16.2
通讯作者：
PRICE, DL
中科院分区：
文献类型：
--
作者：
WONG, PC;PARDO, CA;PRICE, DL
铜/锌超氧化物歧化酶 (SOD1) 突变会导致部分家族性肌萎缩侧索硬化症病例。累积其中一种突变蛋白（G37R）的四系小鼠会出现严重的进行性运动神经元疾病。在突变体积累水平较低时，病理仅限于较低的运动神经元，而较高水平会导致更严重的异常并影响各种其他神经元群体。最明显的细胞异常是轴突和树突中存在膜边界液泡，这些液泡似乎源自退化的线粒体。由于以相似和更高水平表达野生型人类 SOD1 的多个品系的小鼠不会表现出疾病，因此表达 G37R 突变型 SOD1 的小鼠中的疾病一定是由于突变酶获得了不利特性，而不是 SOD1 活性的升高或丧失。
Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease. At lower levels of mutant accumulation, pathology is restricted to lower motor neurons, whereas higher levels cause more severe abnormalities and affect a variety of other neuronal populations. The most obvious cellular abnormality is the presence in axons and dendrites of membrane-bounded vacuoles, which appear to be derived from degenerating mitochondria. Since multiple lines of mice expressing wild-type human SOD1 at similar and higher levels do not show disease, the disease in mice expressing the G37R mutant SOD1 must arise from the acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity.