DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations
DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations
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DOI：
10.1016/j.brainres.2006.02.102
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发表时间：
2006-05-09
期刊：
影响因子：
2.9
通讯作者：
Robertson, Harold A.
中科院分区：
文献类型：
--
作者：
Crocker, Susan F.;Costain, Willard J.;Robertson, Harold A.
亨廷顿病(HD)是一种遗传性的进行性神经退行性疾病，由亨廷顿蛋白编码基因的CAG重复扩增引起。导致纹状体神经元选择性丢失的潜在神经病理事件尚不清楚。然而，亨廷顿蛋白突变在几个层面上干扰了正常的细胞功能。这种疾病的复杂性使微阵列分析成为一种吸引人的技术，可以开始识别可能有助于病理的常见途径。在这项研究中，提取了表达部分人类亨廷顿病基因的野生型和症状型转基因亨廷顿鼠(R6/2)的纹状体组织，用于基因表达谱分析。我们询问了以前没有用于HD的15K高密度小鼠EST阵列，并在有症状的R6/2小鼠中鉴定出170个显著差异表达的EST。在已知功能的80个基因中，有9个基因此前已被鉴定为HD的改变。71个已知基因首次与HD相关。从这项研究中获得的数据证实并扩展了之前使用DNA微阵列技术对HD遗传模型的观察，揭示了一些以前与HD无关的基因表达的新变化。进一步的生物信息学分析，使用软件构建生物关联图，将注意力集中在胰岛素和TH1介导的细胞因子等蛋白质上，表明它们可能是受影响基因的重要调节因子。这些结果可能有助于深入了解参与HD适应性和病理过程的基因的调控和相互作用。(C)2006爱思唯尔B.V.保留所有权利。
Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function. The complexity of this disease makes microarray analysis an appealing technique to begin the identification of common pathways that may contribute to the pathology. In this study, striatal tissue was extracted for gene expression profiling from wild-type and symptomatic transgenic Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We interrogated a 15 K high-density mouse EST array not previously used for HD and identified 170 significantly differentially expressed ESTs in symptomatic R6/2 mice. Of the 80 genes with known function, 9 genes had previously been identified as altered in HD. 71 known genes were associated with HD for the first time. The data obtained from this study confirm and extend previous observations using DNA microarray techniques on genetic models for HD, revealing novel changes in expression in a number of genes not previously associated with HD. Further bioinformatic analysis, using software to construct biological association maps, focused attention on proteins such as insulin and TH1-mediated cytokines, suggesting that they may be important regulators of affected genes. These results may provide insight into the regulation and interaction of genes that contribute to adaptive and pathological processes involved in HD. (c) 2006 Elsevier B.V. All rights reserved.