Knock-in mouse models of Huntington's disease.
Knock-in mouse models of Huntington's disease.
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DOI：
10.1602/neurorx.2.3.465
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发表时间：
2005-07-01
期刊：
影响因子：
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通讯作者：
Menalled, Liliana B
中科院分区：
文献类型：
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作者：
Menalled, Liliana B
亨廷顿病是一种常染色体显性神经退行性疾病，其特征是运动、认知和精神改变。导致这种致命疾病的突变是编码亨廷顿蛋白的基因编码区内异常扩展且不稳定的 CAG 重复序列。已经建立了许多小鼠模型，这些模型构成了检查疾病发病机制以及开发和评估新疗法的宝贵工具。在这些模型中，基因敲入小鼠提供了人类状况的基因精确复制。基因敲入小鼠的行为、病理、细胞和分子异常的缓慢进展和早期发展使得这些动物对于了解突变引发的早期病理事件很有价值。这篇综述描述了生成的不同敲入模型、从中获得的见解以及它们在开发和测试该疾病的前瞻性治疗方法中的价值。
Huntington's disease is an autosomal dominant neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric alterations. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding huntingtin. Numerous mouse models have been generated that constitute invaluable tools to examine the pathogenesis of the disease and to develop and evaluate novel therapies. Among those models, knock-in mice provide a genetically precise reproduction of the human condition. The slow progression and early development of behavioral, pathological, cellular, and molecular abnormalities in knock-in mice make these animals valuable to understand the early pathological events triggered by the mutation. This review describes the different knock-in models generated, the insight gained from them, and their value in the development and testing of prospective treatments of the disease.