Gurney M E, Pu H, Chiu A Y, Dal Canto M C, Polchow C Y, Alexander D D, Caliendo J, Hentati A, Kwon Y W, Deng H X
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611.
Science. 1994 Jun 17;264(5166):1772-5. doi: 10.1126/science.8209258.
Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.
在大约20%的家族性肌萎缩侧索硬化症（ALS）患者中发现了人类铜锌超氧化物歧化酶（SOD）的突变。在93位甘氨酸被丙氨酸取代的人类SOD高水平表达——这种变化对酶活性影响很小——在转基因小鼠中引发了运动神经元疾病。由于脊髓运动神经元丧失，这些小鼠的一个或多个肢体出现瘫痪，并在5至6个月龄时死亡。结果表明，SOD中的显性功能获得性突变促成了家族性ALS的发病机制。
