Modulation of ATXN1 S776 phosphorylation reveals the importance of allele-specific targeting in SCA1

RNA was isolated from mouse cerebellum at 6 weeks of age in 5 different genotypes; wild-type (WT), Atxn1_154Q/2Q (SCA1), Atxn1_154Q[S776A]/2Q (SCA1 S776A), Atxn1_154Q[S776A]/2Q[S776A] (S776A Double) and Atxn1_2Q[S776A]/2Q[S776A] (homo). After RNA isolation, RNA-seq was performed and gene expression profiles were compared between WT, SCA1, and the S776A mutants. The goal was to determine if mutating the phosphorylation site S776 in the context of spinocerebellar ataxia type 1 (SCA1) is protective. Cerebellar mRNA profiles of 6-week mice in wild-type (WT), Atxn1_154Q/2Q (SCA1), Atxn1_154Q[S776A]/2Q (SCA1 S776A), Atxn1_154Q[S776A]/2Q[S776A] (S776A Double) and Atxn1_2Q[S776A]/2Q[S776A] (homo).本研究从5种不同基因型的6周龄小鼠小脑组织中提取总RNA，所涉及的基因型包括：野生型（wild-type, WT）、Atxn1_154Q/2Q（SCA1，脊髓小脑共济失调1型，spinocerebellar ataxia type 1）、Atxn1_154Q[S776A]/2Q（SCA1 S776A）、Atxn1_154Q[S776A]/2Q[S776A]（S776A Double）及Atxn1_2Q[S776A]/2Q[S776A]（纯合子，homo）。完成RNA提取后，对样本进行RNA测序（RNA-seq），并比较野生型（WT）、SCA1模型与S776A突变体之间的基因表达谱差异。本研究旨在明确：在脊髓小脑共济失调1型（SCA1）的背景下，突变其致病蛋白的磷酸化位点S776是否具有保护作用。本数据集涵盖上述5种基因型6周龄小鼠的小脑mRNA表达谱。