Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
Hum Mol Genet. 2010 Apr 15;19(8):1438-52. doi: 10.1093/hmg/ddq018. Epub 2010 Jan 20.
Evaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel: Affymetrix and Illumina. The data from these two powerful platforms were integrated to create a combined rank list, thereby revealing the identity of additional genes that proved to be differentially expressed between YAC128 and control mice. Using this approach, we identified 13 genes to be differentially expressed between YAC128 and controls which were validated by quantitative real-time PCR in independent cohorts of animals. In addition, we analyzed additional time points relevant to disease pathology: 3, 6 and 9 months of age. Here we present data showing the evolution of changes in the expression of selected genes: Wt1, Pcdh20 and Actn2 RNA levels change as early as 3 months of age, whereas Gsg1l, Sfmbt2, Acy3, Polr2a and Ppp1r9a RNA expression levels are affected later, at 12 and 24 months of age. We also analyzed the expression of these 13 genes in human HD and control brain, thereby revealing changes in SLC45A3, PCDH20, ACTN2, DDAH1 and PPP1R9A RNA expression. Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE19677.
评估纹状体中的转录变化可能是了解导致亨廷顿病（HD）发病机制的表达变化的有效方法。我们使用两种平台平行对 YAC128 转基因 HD 小鼠模型进行了全基因组表达谱分析：Affymetrix 和 Illumina。这两个强大平台的数据被整合到一个综合排名列表中，从而揭示了另外一些被证明在 YAC128 和对照小鼠之间差异表达的基因的身份。使用这种方法，我们鉴定了 13 个在 YAC128 和对照之间差异表达的基因，这些基因在独立的动物队列中通过定量实时 PCR 得到了验证。此外，我们还分析了与疾病病理学相关的其他时间点：3、6 和 9 个月大。在这里，我们展示了数据，显示了选定基因表达变化的演变：Wt1、Pcdh20 和 Actn2 RNA 水平早在 3 个月大时就发生变化，而 Gsg1l、Sfmbt2、Acy3、Polr2a 和 Ppp1r9a RNA 表达水平则在 12 和 24 个月大时受到影响。我们还分析了这些 13 个基因在人类 HD 和对照大脑中的表达，从而揭示了 SLC45A3、PCDH20、ACTN2、DDAH1 和 PPP1R9A RNA 表达的变化。进一步研究这些基因可能揭示导致 HD 发病机制的新途径。DDBJ/EMBL/GenBank 登录号：GSE19677。
