Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
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DOI：
10.1093/hmg/dds399
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发表时间：
2013-01-01
影响因子：
3.5
通讯作者：
Brannstrom, Thomas
中科院分区：
文献类型：
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作者：
Graffmo, Karin S.;Forsberg, Karin;Brannstrom, Thomas
肌萎缩性侧索硬化症（ALS）的常见原因是编码超氧化物歧化酶-1的基因突变。有不断发展的间接证据表明，野生型蛋白也可能具有神经毒性，并且它可能更普遍地参与ALS的发病机制。为了更直接地验证这一命题，我们培养了表达野生型人类超氧化物歧化酶-1的小鼠，其表达率接近于常见的G93A转基因模型中突变型超氧化物歧化酶-1的表达率。这些老鼠患上了类似als的综合症，并在大约370天后患上了绝症。脊髓腹侧神经元的丢失与G93A及其他超氧化物歧化酶-1突变模型相似，在脊髓和大脑中均发现大量聚集的超氧化物歧化酶-1。研究结果表明，野生型人类超氧化物歧化酶-1具有导致小鼠肌萎缩性侧索硬化症的能力，它们支持了这种蛋白质与人类疾病更普遍相关的假设。
A common cause of amyotrophic lateral sclerosis (ALS) is mutations in the gene encoding superoxide dismutase-1. There is evolving circumstantial evidence that the wild-type protein can also be neurotoxic and that it may more generally be involved in the pathogenesis of ALS. To test this proposition more directly, we generated mice that express wild-type human superoxide dismutase-1 at a rate close to that of mutant superoxide dismutase-1 in the commonly studied G93A transgenic model. These mice developed an ALS-like syndrome and became terminally ill after around 370 days. The loss of spinal ventral neurons was similar to that in the G93A and other mutant superoxide dismutase-1 models, and large amounts of aggregated superoxide dismutase-1 were found in spinal cords, but also in the brain. The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.