title: Expression analysis of novel striatal-enriched genes in Huntington disease.
abstract: Selective degeneration of striatal neurons is a pathologic hallmark of Huntington disease (HD). The exact mechanism(s) behind this specific neurodegeneration is still unknown. Expression studies of diseased human post-mortem brain, as well as different mouse models exhibiting striatal degeneration, have demonstrated changes in the expression of many important genes with a large proportion of changes being observed in the striatal-enriched genes. These investigations have raised questions about how enrichment of particular transcripts in the striatum can lead to its selective vulnerability to neurodegeneration. Monitoring the expression changes of striatal-enriched genes during the course of the disease may be informative about their potential involvement in selective degeneration. In this study, we analyzed a Serial Analysis of Gene Expression (SAGE) database (www.mouseatlas.org) and compared the mouse striatum to 18 other brain regions to generate a novel list of striatal-enriched transcripts. These novel striatal-enriched transcripts were subsequently evaluated for expression changes in the YAC128 mouse model of HD, and differentially expressed transcripts were further examined in human post-mortem caudate samples. We identified transcripts with altered expression in YAC128 mice, which also showed consistent expression changes in human post-mortem tissue. The identification of novel striatal-enriched genes with altered expression in HD offers new avenues of study, leading towards a better understanding of specific pathways involved in the selective degeneration of striatal neurons in HD.
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
authors.forename: Gelareh
authors.initials: G
authors.lastname: Mazarei
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Neal
authors.forename: Kristina
authors.initials: K
authors.lastname: Becanovic
authors.forename: Ruth
authors.initials: R
authors.lastname: Luthi-Carter
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Simpson
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D051379:Mice