Transcriptional profiling of striatum from a zQ175 KI mouse model of Huntington's disease with or without homozygous knockout of the Msh3 gene

Previous studies have suggested a strong association between lower MSH3 expression, reduced somatic repeat expansion, and slower disease onset and progression. The effects of a homozygous knock-out in the Msh3 gene on transcriptome phenotypes in striatum in six-month-old WT and zQ175 mice were studied. Striatum was isolated from 6-month-old mice. Transcriptomic analysis (RNASeq) was performed on four genotypes with 8 replicates per genotype: WT (WT for Htt and Msh3), zQ175 (zQ175 for Htt, WT for Msh3), WT.Msh3.HOM (WT for Htt, Homozygous for Msh3 KO), and zQ175.Msh3.HOM (zQ175 for Htt, Homozygous for Msh3 KO). RNASeq analysis was performed on samples from the striatum tissues of 6-month-old mice with one of the following four genotypes: WT, WT.Msh3.HOM, zQ175, zQ175.Msh3.HOM. N = 8 per group (4M/4F except zQ175.Msh3.HOM which had 5M/3F).既往研究表明，MutS同源蛋白3（MSH3）表达下调、体细胞重复扩增减少与疾病发病延迟及进展放缓之间存在显著关联。本研究探究了Msh3基因纯合敲除对6月龄野生型（WT）与zQ175小鼠纹状体转录组表型的影响。实验材料取自6月龄小鼠的纹状体组织。本研究对四种基因型的样本开展转录组测序（RNASeq）分析，每种基因型设置8个生物学重复：四种基因型分别为仅Htt与Msh3位点均为野生型的WT、仅Htt携带zQ175突变而Msh3位点为野生型的zQ175、Htt位点为野生型且Msh3为纯合敲除的WT.Msh3.HOM，以及Htt携带zQ175突变且Msh3为纯合敲除的zQ175.Msh3.HOM。本次RNASeq分析的样本均来自6月龄小鼠的纹状体组织，对应以下四种基因型之一：WT、WT.Msh3.HOM、zQ175及zQ175.Msh3.HOM。每组样本量均为8只：除zQ175.Msh3.HOM组为5雄3雌外，其余各组均为4雄4雌。