Extensive splicing changes in an ALS/FTD transgenic mouse model overexpressing cytoplasmic fused in sarcoma

Daisuke Ito, Ryota Taguchi, Maki Deguchi, Hideaki Ogasawara, Eiji Inoue

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Mutations in RNA-binding proteins (RBPs) such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent evidence suggests that RNA dysregulation mediated by aberrant RBPs may play a critical role in neurodegeneration, but the underlying molecular mechanisms are largely unknown. In this study, we performed whole transcriptome profiling of various brain tissues of a transgenic (Tg) mouse model of ALS/FTD overexpressing the exogenous nuclear localization signal deletion mutant of human FUS (ΔNLS-FUS) to investigate changes associated with the early stages of ALS/FTD. Although there were not many differences in expression profiles between wild-type and Tg mice, we found that Sema3g was significantly upregulated in the frontal cortex and hippocampus of Tg mice. Interestingly, analysis of alternative splicing events identified widespread exons that were differentially regulated in Tg mice in a tissue-specific manner. Our study thus identified aberrant splicing regulation mediated by mutant FUS during the early stages of ALS/FTD. Targeting this aberrant splicing regulation represents a potential therapeutic strategy for ALS/FTD.

本文言語English
論文番号4857
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • 一般

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