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

Develop and analysis for chromosome mutant mice

Research Project

Project/Area Number 17K07119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nomura Jun  国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (70406528)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自閉症 / 染色体操作 / 動物モデル / 統合失調症 / てんかん / 薬理 / 染色体工学 / コピー数多型 / 精神疾患 / 発達障害 / モデルマウス / スパイン / GABA / コピー数変異 / ヒト型疾患モデル動物 / コピー数多型(CNV) / ゲノム編集
Outline of Final Research Achievements

In this term, we newly developed (chromosome mutant) animal models of autism spectrum disorder (ASD) for human 15q13.3 deletion, and GABAR cluster deletion in 15q11-q13 locus.
In particular, 15q13.3 model mice showed social deficits which mimic core symptom of patients with ASD. Simultaneously, we performed seizure assay as pharmacological test using animal model of 15q25.2-25.3 deletion and 15q13.3 deletion mice. In this analysis we applied non-liquid gas-system which efficiently cause seizure-like symptoms. In this assay, 15q13.3 heterozygote deletion mice didn't show clear changes, however, 15q13.3 homozugote mice increased frequency of generalized seizures. We also analyzed gender difference using 15q13.3 heterozygte and homozygote mice. However, no differences were observed in this assay. Thus, we concluded that 15q13.3 locus is associated with both ASD-like symptoms and seizure, but gender may not associated with these symptoms.

Academic Significance and Societal Importance of the Research Achievements

コミュニケーションの障害をコア症状とする自閉スペクトラム症は,単一遺伝子の変異とともに染色体レベルの欠失や重複でも相関が認められている.疾患の理解,創薬において動物モデルは必須であるが,染色体変異を反映したモデルは僅かである.このため本研究ではヒト染色体と相同性の高い15q25.2-25-3欠失モデルとともに,15q13.3欠失モデル,15q11-13内のGABA受容体のクラスターを欠失したモデルを新規で作製した.また自閉症患者ではてんかん発作も高頻度に認められるが,その関係を15q13.3モデルを用い解析したところ,当該染色体領域との有意な相関を認めた.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Characterizing vulnerable brain areas and circuits in mouse models of autism: Towards understanding pathogenesis and new therapeutic approaches.2018

    • Author(s)
      Hui K, Katayama Y, Nakayama KI, Nomura J, Sakurai T.
    • Journal Title

      Neurosci. Biobehav. Rev.

      Volume: 印刷中 Pages: 30121-0

    • DOI

      10.1016/j.neubiorev.2018.08.001

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Comprehensive analysis identified CNV- and cell type specific vulnerability across psychiatric disorders2020

    • Author(s)
      Jun Nomura
    • Organizer
      Takeda Science Foundation, The 10th Takeda Science Foundation International Symposium on PharmaSciences
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト染色体15q13.3コピー数多型モデルの統合的解析 ーヒト染色体15q13.3コピー数多型モデルのトランスクリプトーム解析ー2019

    • Author(s)
      Jun Nomura
    • Organizer
      喫煙財団研究発表会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phenotypic analysis of a mouse model for 15q25.2-25.3 deletion syndrome.2017

    • Author(s)
      Nomura, Jun; Kanda, Akifumi; Ellegood, Jacob; Lerch, Jason; Sotomaru, Yusuke; Takumi, Toru
    • Organizer
      26th Annual Meeting of the International Behavioral Neuroscience Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain structural and behavioral abnormalities in a mouse model for 15q25.2-25.3 microdeletion syndrome2017

    • Author(s)
      Nomura, Jun; Kanda, Akifumi; Ellegood, Jacob; Lerch, Jason; Sotomaru, Yusuke; Takumi, Toru
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Book] 自閉症学2019

    • Author(s)
      野村淳,内匠透
    • Total Pages
      234
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi