Identification of TDP-43 related genes using gene trap

• Project/Area Number: 16K15481
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Hiroshima University
• Principal Investigator: Kawakami Hideshi 広島大学, 原爆放射線医科学研究所, 教授 (70253060)
• Co-Investigator(Kenkyū-buntansha): 森野 豊之 広島大学, 原爆放射線医科学研究所, 准教授 (10397953)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: TDP-43 / 筋萎縮性側索硬化症 / 脳神経疾患 / 神経科学 / 遺伝学

Outline of Final Research Achievements

Aggregates of TAR DNA-binding protein of 43 kDa(TDP-43)are characteristic in motorneuron in amyotrophic lateral sclerosis. To identify genes influencing TDP-43 aggregate formation, we infected lentivirus from the library with CRISPR and the recognition sequence and destroy genes. We expressed TDP-43 with eGFP and isolated cells with enhanced signals by cell sorter. We sequenced DNA extracted from cells by next-generation sequencer, and identified 30 genes as TDP-43 aggregate formation related.

Research Products

• [Journal Article] Multiple proteinopathies in familial ALS cases with optineurin mutation. (2017)
  • Author(s): Ayaki T, Ito H, Komure O, Kamada M, Nakamura M, Wate R, Kusaka H, Yamaguchi Y, Li F, Kawakami H, Urushitani M, Takahashi R
  • Journal Title: J Neuropathol Exp Neurol Volume: 77 Issue: 2 Pages: 128-138
  • DOI: 10.1093/jnen/nlx109
  • Peer Reviewed