Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse
Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse
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DOI：
10.1016/s0092-8674(00)80464-x
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发表时间：
1997-12-12
期刊：
影响因子：
64.5
通讯作者：
Detloff, PJ
中科院分区：
文献类型：
--
作者：
Ordway, JM;TallaksenGreene, S;Detloff, PJ
导致几种人类神经退行性疾病的突变是翻译的CAG重复序列超出正常大小范围的扩展。为了解决重复上下文的作用，我们已经引入了一个146单位的CAG重复到小鼠次黄嘌呤磷酸核糖转移酶基因（Hprt）。突变小鼠表达一种形式的HPRT蛋白，其中包含一个长的多聚谷氨酰胺重复。这些小鼠发展出类似于人类翻译的CAG重复障碍的表型。含有重复序列的小鼠表现出迟发性神经系统表型，其进展为过早死亡。受影响的小鼠中存在神经元核内包涵体。我们的结果表明，CAG重复序列不需要位于经典重复障碍基因之一中就能产生神经毒性作用。
The mutations responsible for several human neurodegenerative disorders are expansions of translated CAG repeats beyond a normal size range. To address the role of repeat context, we have introduced a 146-unit CAG repeat into the mouse hypoxanthine phosphoribosyltransferase gene (Hprt). Mutant mice express a form of the HPRT protein that contains a long polyglutamine repeat. These mice develop a phenotype similar to the human translated CAG repeat disorders. Repeat containing mice show a late onset neurological phenotype that progresses to premature death. Neuronal intranuclear inclusions are present in affected mice. Our results show that CAG repeats do not need to be located within one of the classic repeat disorder genes to have a neurotoxic effect.