Serra Heliane G, Byam Courtney E, Lande Jeffrey D, Tousey Susan K, Zoghbi Huda Y, Orr Harry T
Department of Laboratory Medicine and Pathology, University of Minnesota, Mayo Mail Code 206, Minneapolis, Minnesota 55455, USA.
Hum Mol Genet. 2004 Oct 15;13(20):2535-43. doi: 10.1093/hmg/ddh268. Epub 2004 Aug 18.
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine repeat within the disease protein, ataxin 1. To elucidate cellular pathways involved in SCA1, we used DNA microarrays to determine the pattern of gene expression in SCA1 transgenic mice at two specific times in the disease process; 5 weeks, a timepoint prior to onset of pathology, and 12 weeks, at the midpoint of the disease progression. Taking advantage of the availability of three SCA1 transgenic mouse lines, each expressing a different form of ataxin-1, we utilized a strategy that resulted in the identification of a limited number of genes with an altered pattern of expression specific to the development of disease. By comparing the pattern of gene expression in the SCA1 ataxic B05-ataxin-1[82Q] transgenic mouse line with those seen in two non-ataxic lines, A02-ataxin-1[30Q] and K772T-[82Q], nine genes were identified whose expression was consistently altered in the cerebellum of B05[82Q] mice at 5 and 12 weeks of age. Interestingly, five of the genes in this group form a biological cohort centered on glutamate signaling pathways in Purkinje cells.
1型脊髓小脑共济失调（SCA1）是一种神经退行性疾病，由疾病蛋白ataxin 1内的多聚谷氨酰胺重复序列扩增引起。为了阐明参与SCA1的细胞途径，我们使用DNA微阵列来确定SCA1转基因小鼠在疾病过程中的两个特定时间点的基因表达模式；5周，这是病理发作前的一个时间点，以及12周，在疾病进展的中点。利用三种SCA1转基因小鼠品系的可得性，每个品系表达不同形式的ataxin-1，我们采用了一种策略，该策略导致鉴定出有限数量的基因，其表达模式的改变特定于疾病的发展。通过比较SCA1共济失调B05-ataxin-1[82Q]转基因小鼠品系与两个非共济失调品系A02-ataxin-1[30Q]和K772T-[82Q]中观察到的基因表达模式，鉴定出九个基因，其表达在B05[82Q]小鼠5周和12周龄时的小脑中持续改变。有趣的是，该组中的五个基因形成了一个以浦肯野细胞中的谷氨酸信号通路为中心的生物学群组。
