Establishment of ALS model by artificial RNA-binding proteins related to ALS proteinopathies.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07534
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Keio University
• Principal Investigator: ITO Daisuke 慶應義塾大学, 医学部(信濃町), 准教授 (80286450)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 筋萎縮性側索硬化症 / 前頭側頭型認知症 / TDP-43 / FUS

Outline of Final Research Achievements

The aim of this study was to generate a novel ALS model, knocked-in mouse of artificially designing cDNA harboring with the characteristics of the ALS causative genes causing ALS and introducing into the ROSA26 locus to examined their cytotoxicity in vivo.
We were able to obtain a line of ALS artificial gene knock-in mice. Currently, we are planning to breed them. On the other hand, from the analysis of our established ALS model mouse (△NLS-FUS transgenic), we found that a wide variety of splicing changes were observed in the brain and spinal cord and also that semaphorin 3G, which is required for synaptic plasticity, was upregulated in this mouse.

Free Research Field

神経内科

Academic Significance and Societal Importance of the Research Achievements

本研究により、ALS病態誘導人工遺伝子が神経変性のトリガーとなることをin vivoで証明するとともに、運動ニューロンの選択的変性の分子機構をin vivoレベルで解析が可能となり、新規治療戦略の確立、薬剤の評価への利用が期待できる.
また、△NLS-FUSトランスジェニックマウスより見出されたSemaphorin 3Gは、バイオマーカーへの応用や治療ターゲットにつながることが期待される.