...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
【24h】

Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions

机译：尽管存在广泛的神经元亨廷顿蛋白包涵体，但体内没有行为异常和神经变性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (≈120) under the control of the endogenous human promoter (shortstop). Frequent and widespread htt inclusions occur early in shortstop mice. Despite these inclusions, shortstop mice display no clinical evidence of neuronal dysfunction and no neuronal degeneration as determined by brain weight, striatal volume, and striatal neuronal count. These results indicate that htt inclusions are not pathogenic in vivo. In contrast, the full-length yeast artificial chromosome (YAC) 128 model with the identical polyglutamine length and same level of transgenic protein expression as the shortstop demonstrates significant neuronal dysfunction and loss. In contrast to the YAC128 mouse, which demonstrates enhanced susceptibility to excitotoxic death, the shortstop mouse is protected from excitotoxicity, providing in vivo evidence suggesting that neurodegeneration in Huntington disease is mediated by excitotoxic mechanisms.
机译：我们偶然地建立了一种小鼠，该小鼠在内源性人类启动子（游击手）的控制下表达具有扩展的聚谷氨酰胺重复序列（≈120）的N端人类亨廷顿蛋白（htt）片段。频繁且广泛的HTT夹杂物在游击手小鼠中较早发生。尽管有这些内含物，但游击手小鼠并未显示出神经元功能异常的临床证据，也没有显示出由脑重量，纹状体体积和纹状体神经元计数确定的神经元变性。这些结果表明，htt内含物在体内不是致病的。相反，全长酵母人工染色体（YAC）128模型具有与游击手相同的多聚谷氨酰胺长度和相同的转基因蛋白表达水平，显示出明显的神经元功能障碍和丧失。与表现出对兴奋性毒性死亡的敏感性增强的YAC128小鼠相反，该速发性小鼠受到了兴奋性毒性的保护，提供了体内证据，表明亨廷顿病的神经退行性疾病是由兴奋性毒性机制介导的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号