Establishing ES cell lines for neurological diseases using CRISPR/Cas9 systems

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670438
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: WATASE Kei 東京医科歯科大学, 脳統合機能研究センター, 准教授 (30376800)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: 遺伝子組換えマウス / 神経疾患 / パーキンソン病 / リソソーム

Outline of Final Research Achievements

Recently a missense mutation in VPS35 (D620N) has been shown to cause an autosomal dominant late-onset form of Parkinson disease (PARK17) but molecular pathogenesis of PARK17 remains elusive. In order to model PARK17 in mice and elucidate its molecular pathogenesis, I have successfully generated the knockin mice carrying the mutation homologous to D620N as well as the mice with an NHEJ-mediated deletion or insertion mutation in the murine Vps35 gene by CRISPR-Cas9 method. Using the same methodology, I have also succeeded in generating knockin mice which express constitutively active form of Tfeb, which is known as a master regulator of lysosomal biogenesis.

Free Research Field

神経遺伝学