Early onset deficits on the delayed alternation task in the Hdh^Q92 knock-in mouse model of Huntington's disease

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• 作者：R.C. Trueman^a ; ^{TruemanRC@cf.ac.uk} ; L. Jones^b ; S.B. Dunnett^a ; S.P. Brooks^a
• 关键词：Huntington's disease ; HdhQ92 mice ; Knock-in mice ; Operant tests ; 9-Hole box ; Delayed alternation ; Cognitive impairment
• 刊名：Brain Research Bulletin
• 出版年：2012
• 期刊代码：9_03619230
• 类别：neu
• 出版时间：1 June, 2012
• 卷：88
• 期：2-3
• 页码：156-162
• 文件大小：336 K

摘要

A number of genetic mouse models of Huntington's disease have been created, in order to examine the pathogenesis of Huntington's disease and to test potential therapeutics. In the present study we demonstrate that the full-length knock-in homozygote Hdh^Q92 mice exhibit impairments at 5 months of age on the delayed alternation task, conducted in 9-hole operant chambers. This test is sensitive to cortico-striatal dysfunction and demonstrates again that although Hdh^Q92 mice do not display an overt motor phenotype, they do exhibit clear impairments that can be related to deficits seen in HD patients. This indicates that if appropriately sensitive tasks are used, the more subtle and specific Hdh^Q92 knock-in model could be of use for the examination of pathogenic mechanisms in Huntington's disease and to test potential therapeutics.