Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
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DOI：
10.1016/s0092-8674(00)80513-9
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发表时间：
1997-08-08
期刊：
影响因子：
64.5
通讯作者：
Bates, GP
中科院分区：
文献类型：
--
作者：
Davies, SW;Turmaine, M;Bates, GP
亨廷顿病(HD)是由CAG/多谷氨酰胺重复序列扩张引起的越来越多的人类神经退行性疾病之一。这种突变发生在一种功能未知的基因中，该基因在广泛的组织中表达。在HD中观察到的延迟起病、选择性的神经病理模式和细胞死亡的分子机制尚未被描述。我们观察到，携带(GAG)(115)到(CAG)(156)重复扩增的人HO基因外显子1转基因小鼠在形成神经表型之前，会出现明显的神经元核内包涵体，其中包含亨廷顿蛋白和泛素。在转基因小鼠中，这些包涵体的出现，随后是神经元核内的特征性形态变化，与HD患者活检材料中观察到的核异常惊人地相似。
Huntington's disease (HD) is one of an increasing number of human neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The mutation occurs in a gene of unknown function that is expressed in a wide range of tissues. The molecular mechanism responsible for the delayed onset, selective pattern of neuropathology, and cell death observed in HD has not been described. We have observed that mice transgenic for exon 1 of the human Ho gene carrying (GAG)(115) to (CAG)(156) repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype. The appearance in transgenic mice of these inclusions, followed by characteristic morphological change within neuronal nuclei, is strikingly similar to nuclear abnormalities observed in biopsy material from HD patients.