Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice
Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice
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DOI：
10.1006/nbdi.1998.0178
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发表时间：
1998-07-01
影响因子：
6.1
通讯作者：
Hoffman, PN
中科院分区：
文献类型：
--
作者：
Borchelt, DR;Wong, PC;Hoffman, PN
超氧化物歧化酶1（SOD 1）是一种广泛表达的酶，可解毒超氧化物自由基并参与铜稳态。这种酶的突变与家族性肌萎缩性侧索硬化症（FALS）的常染色体显性病例子集有关，这是一种以运动神经元选择性变性为特征的疾病。高水平表达FALS突变体人（Hu）SOD1的转基因小鼠发生运动神经元疾病，表明突变体Hu SOD1获得对运动神经元特别有毒的特性。在这份报告中，我们表明，转基因小鼠表达胡SOD1与G37 R的FALS突变，但不是小鼠表达野生型酶，发展局灶性增加脊髓运动神经元的近端轴突的免疫反应性。这种SOD1免疫反应性和对低磷酸化神经丝H表位的免疫反应性被发现邻近轴突中的小空泡。使用代谢放射性标记方法，我们表明，突变体G37 R HuSOD 1以及内源性小鼠SOD 1在坐骨神经的运动和感觉轴突中的慢成分B中顺行转运。总之，这些研究结果表明，顺行运输突变SOD 1可能会发挥局部作用，损害运动轴突。(C)北京：科学出版社.
Superoxide dismutase 1 (SOD1), a ubiquitously expressed enzyme, detoxifies superoxide radicals and participates in copper homeostasis. Mutations in this enzyme have been linked to a subset of autosomal dominant cases of familial amyotrophic lateral sclerosis (FALS), a disorder characterized by selective degeneration of motor neurons. Transgenic mice expressing FALS mutant human (Hu) SOD1 at high levels develop a motor neuron disease, indicating that mutant Hu SOD1 gains properties that are particularly toxic to motor neurons. In this report, we demonstrate that transgenic mice expressing Hu SOD1 with the G37R FALS mutation, but not mice expressing wild-type enzyme, develop focal increases in immunoreactivity in the proximal axons of spinal motor neurons. This SOD1 immunoreactivity and immunoreactivity to hypophosphorylated neurofilament H epitopes are found adjacent to small vacuoles in axons. Using metabolic radiolabeling methods, we show that mutant G37R HuSOD1 as well as endogenous mouse SOD1 are transported anterograde in slow component b in motor and sensory axons of the sciatic nerve. Together, these findings suggest that anterogradely transported mutant SOD1 may act locally to damage motor axons. (C) 1998 Academic Press.