Couillard-Després S, Zhu Q, Wong P C, Price D L, Cleveland D W, Julien J P
Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Montreal H3G 1A4 Canada.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9626-30. doi: 10.1073/pnas.95.16.9626.
To investigate the role of neurofilaments in motor neuron disease caused by superoxide dismutase (SOD1) mutations, transgenic mice expressing a amyotrophic lateral sclerosis-linked SOD1 mutant (SOD1(G37R)) were mated with transgenic mice expressing human neurofilament heavy (NF-H) subunits. Unexpectedly, expression of human NF-H transgenes increased by up to 65%, the mean lifespan of SOD1(G37R) mice. Microscopic examination corroborated the protective effect of NF-H protein against SOD1 toxicity. Although massive neurodegeneration occurred in 1-yr-old mice expressing SOD1(G37R) alone, spinal root axons and motor neurons were remarkably spared in doubly SOD1(G37R);NF-H-transgenic littermates.
为了研究神经丝在由超氧化物歧化酶（SOD1）突变引起的运动神经元疾病中的作用，将表达与肌萎缩侧索硬化相关的SOD1突变体（SOD1(G37R)）的转基因小鼠与表达人神经丝重链（NF-H）亚基的转基因小鼠进行交配。出乎意料的是，人NF-H转基因的表达使SOD1(G37R)小鼠的平均寿命延长了65%。显微镜检查证实了NF-H蛋白对SOD1毒性的保护作用。虽然仅表达SOD1(G37R)的1岁小鼠发生了大量神经退行性变，但在双转基因SOD1(G37R);NF-H的同窝仔鼠中，脊神经根轴突和运动神经元明显未受影响。
