Establishing autism model cells by gene editing technology

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Nakayama Atsuo 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, 部長 (50227964)
• Co-Investigator(Kenkyū-buntansha): 松木 亨 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, 主任研究員 (90332329)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: iPS細胞 / ゲノム編集 / 自閉症 / ヒト神経細胞

Outline of Final Research Achievements

Induced pluripotent stem cells (IPSCs) enabled detailed analyses of human neurons in CNS disorders. However, due to complex genetic abnormalities found in ASD patients, and due to various genetic backgrounds of the human species, the differences between neurons derived from patients' iPSCs and those from control iPSCs can not be readily regarded as a result of genetic alterations causing ASD. Applying genome editing technique, we introduced a single ASD gene disruption in iPSCs, otherwise the identical genetic background with parental iPSCs. We established two independent 610B1 iPSC colones with the NLGN4X gene disruptions. Both clones as well as parental 610B1 cells could not be differentiated to neurons, even by a couple of modified differentiation protocols. Thus, we could not compared neuronal phenotypes of ASD model iPSCs with those of parental iPSCs. We then made NLGN4X KO clones of two other iPSCs that have high efficacy of neuronal differentiation. Analyses are in progress.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

自閉症の原因遺伝子は２００以上あると言われており、その変異一つ一つがどのような神経細胞の異常を引き起こすのかは必ずしも明らかになっていない。個々の遺伝子の機能を明らかにするためには、遺伝学的背景を揃えた上での神経細胞での比較検討が必要となる。今回標準iPS細胞にゲノム編集の技術で自閉症原因遺伝子のみの変異を引き起こしたiPS細胞のクローンが得られたことで、自閉症原因遺伝子の機能障害による神経細胞異常を詳細に明らかにすることが可能となる。さらにはその異常を改善するための薬物開発に利用することも可能となる。