Peripherin is not a contributing factor to motor neuron disease in a mouse model of amyotrophic lateral sclerosis caused by mutant superoxide dismutase.
Peripherin is not a contributing factor to motor neuron disease in a mouse model of amyotrophic lateral sclerosis caused by mutant superoxide dismutase.
复制标题
在由突变型超氧化物歧化酶引起的肌萎缩侧索硬化症小鼠模型中，外周蛋白不是运动神经元疾病的促成因素。
DOI：
10.1016/s0969-9961(03)00036-6
复制
发表时间：
2003
影响因子：
6.1
通讯作者：
Julien,Jean-Pierre
中科院分区：
文献类型：
--
作者：
Larivière,RoxanneC;Beaulieu,Jean-Martin;Nguyen,MinhDang;Julien,Jean-Pierre
Peripherin是在与肌萎缩侧索硬化症（ALS）相关的轴突球体中检测到的III型中间丝蛋白。在转基因小鼠和来自外周蛋白转基因胚胎的培养神经元细胞中，外周蛋白的过表达诱导脊髓运动神经元在衰老过程中变性。在这里，我们调查外周蛋白是否是一个贡献者的发病机制，在小鼠过表达突变型超氧化物歧化酶1（SOD 1G 37 R）基因与家族性ALS。这是通过生成和分析过表达外周蛋白转基因（G37 R;TgPer小鼠）或缺乏内源性外周蛋白基因（G37 R;Per−/−小鼠）的SOD 1G 37 R小鼠来完成的。令人惊讶的是，外周蛋白表达的上调或抑制对SOD 1G 37 R小鼠的疾病发作、死亡率和运动神经元损失没有影响。这些结果提供了令人信服的证据，外周蛋白不是与突变SOD 1毒性相关的运动神经元变性的关键贡献者。
Peripherin is a type III intermediate filament protein detected in axonal spheroids associated with amyotrophic lateral sclerosis (ALS). The overexpression of peripherin induces degeneration of spinal motor neurons during aging in transgenic mice and in cultured neuronal cells derived from peripherin transgenic embryos. Here, we investigated whether peripherin is a contributor of pathogenesis in mice overexpressing a mutant superoxide dismutase 1 (SOD1G37R) gene linked to familial ALS. This was done by the generation and analysis of SOD1G37Rmice that either overexpress a peripherin transgene (G37R;TgPer mice) or lack the endogenous peripherin gene (G37R;Per−/− mice). Surprisingly, upregulation or suppression of peripherin expression had no effects on disease onset, mortality, and loss of motor neurons in SOD1G37Rmice. These results provide compelling evidence that peripherin is not a key contributor of motor neuron degeneration associated with toxicity of mutant SOD1.