• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishing autism model cells by gene editing technology

Research Project

Project/Area Number 16K10202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionInstitute 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
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsiPS細胞 / ゲノム編集 / 自閉症 / ヒト神経細胞 / ニューロリギン4 / ニューロロギン4 / 幹細胞
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (3 results)

  • [Journal Article] Identification of novel compound heterozygous mutations in ACO2 in a patient with progressive cerebral and cerebellar atrophy2019

    • Author(s)
      Masahide Fukada, Keitaro Yamada, Shima Eda, Ken Inoue, Chihiro Ohba, Naomichi Matsuzono, Hirotomo Saitsu, Atsuo Nakayama
    • Journal Title

      Molecular Genetics and Genomic Medicine

      Volume: 7 Issue: 7

    • DOI

      10.1002/mgg3.698

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] WNT10A variants isolated from Japanese patients with congenital tooth agenesis2017

    • Author(s)
      Machida J., Goto H., Tatematsu T., Shibata A., Miyachi H., Takahashi K., Izumi H., Nakayama A., Shimozato K., Tokita Y.
    • Journal Title

      Hum Genome Var

      Volume: 9 Issue: 1 Pages: 17047-17047

    • DOI

      10.1038/hgv.2017.47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Nuclear Localilzation Signals in the Human Homeoprotein, MSX12017

    • Author(s)
      Shibata A., Machida J., Yamaguchi S., Kimura M., Tatematsu T., Miyachi H., Nakayama A., Shimozato K., Tokita Y
    • Journal Title

      Biochem Cell Biol

      Volume: - Issue: 4 Pages: 483-489

    • DOI

      10.1139/bcb-2017-0263

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dopaminergic abnormalities in Hdac6-deficient mice.2016

    • Author(s)
      Fukada M., Nakayama A., Mamiya T., Yao TP., Kawaguchi Y.
    • Journal Title

      Neuroparmacology

      Volume: 110 Pages: 470-479

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterisation of novel RUNX2 mutation with alanine tract expansion from Japanese cleidocranial dysplasia patient.2016

    • Author(s)
      Shibata A., Machida J., Yamaguchi S., Kimura M., Tatematsu T., Miyachi H, Matsushita M., Kitoh H., Ishiguro N., Nakayama A., Higashi Y., Shimozato K., Tokita Y.
    • Journal Title

      Mutagenesis

      Volume: 31 Pages: 61-67

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Stk25 and MST3 act on neuronal polarization and migration in a compensation manner.2018

    • Author(s)
      松木亨、飯尾明生、上田昌史、戸谷明恵、中山敦雄
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 自閉症関連因子TSC2の可逆的アセチル化による機能制御2018

    • Author(s)
      川口禎晴、深田斉秀、竹島京子、中山敦雄
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SON haploinsufficiency, which is causing an intellectual disability, dysregulates neuronal migration in the brain of mouse embryo2018

    • Author(s)
      Masahide Ueda, Tohru Matsuki, Shima Eda, Atsuo Nakayama
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi