C‐terminal deletion of the atrophin‐1 protein results in growth retardation but not neurodegeneration in mice
C‐terminal deletion of the atrophin‐1 protein results in growth retardation but not neurodegeneration in mice
复制标题
肌萎缩蛋白-1 蛋白 C 端缺失会导致小鼠生长迟缓，但不会导致神经退行性变
DOI：
10.1002/dvdy.22063
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发表时间：
2009
影响因子：
2.5
通讯作者：
R. Xu
中科院分区：
文献类型：
--
作者：
Juehua Yu;M. Ying;Zhuang Yuan;Tian Xu;Min Han;Xiaohui Wu;R. Xu
齿状红核-苍白球路易体萎缩症 (DRPLA) 是一种显性遗传性神经退行性疾病，由 Atropin-1 蛋白中聚谷氨酰胺 (poly-Q) 重复序列的扩增引起。 Poly-Q 扩增的人 Atropin-1 的异位表达足以在小鼠中诱导 DRPLA 表型。然而，目前尚不清楚poly-Q扩展的主要作用是否是由于对野生型Atropin-1蛋白的功能干扰造成的，这种蛋白存在于患者和转基因小鼠中。在这里，我们报告了 Atropin-1 靶向等位基因的生成和分析，该等位基因表达缺乏 Poly-Q 重复序列和后续 C 末端肽的截短蛋白。纯合突变体表现出生长迟缓和进行性男性不育，但没有明显的神经变性迹象。此外，突变等位基因既不会阻止也不会增强由poly-Q扩展转基因引起的神经退行性表型。这些结果支持这样的模型：poly-Q 扩展的 Atropin-1 蛋白以独立于与野生型 Atropin-1 蛋白的任何功能相互作用的方式引起 DRPLA。发展动力学 238:2471–2478, 2009。© 2009 Wiley‐Liss, Inc.
Dentatorubral‐pallidoluysian atrophy (DRPLA) is a dominant hereditary neurodegenerative disorder caused by the expansion of a poly‐glutamine (poly‐Q) repeat in Atrophin‐1 protein. Ectopic expression of a poly‐Q expanded human Atrophin‐1 is sufficient to induce DRPLA phenotypes in mice. However, it is still unclear whether the dominant effect of poly‐Q expansion is due to the functional interference with wild‐type Atrophin‐1 proteins, which exist in both patients and transgenic mice. Here we report the generation and analysis of an Atrophin‐1 targeting allele that expresses a truncated protein lacking both the poly‐Q repeat and following C‐terminal peptides. Homozygous mutants exhibit growth retardation and progressive male infertility, but no obvious signs of neurodegeneration. Moreover, the mutant allele neither blocked nor enhanced the neurodegenerative phenotypes caused by a poly‐Q expanded transgene. These results support the model that poly‐Q expanded Atrophin‐1 proteins cause DRPLA in a manner independent of any functional interaction with wild‐type Atrophin‐1 proteins. Developmental Dynamics 238:2471–2478, 2009. © 2009 Wiley‐Liss, Inc.
核和核外polyQ对亨廷顿病小鼠模型神经表型的贡献
影响因子：
3.5
作者：
Benn, CL;Landles, C;Bates, GP
通讯作者：
Bates, GP
DOI：
10.1016/j.bbrc.2005.10.186
发表时间：
2006-01-06
影响因子：
3.1
作者：
Kiehl, TR;Nechiporuk, A;Pulst, SM
通讯作者：
Pulst, SM