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有芯小胞トラフィッキング異常による精神・神経疾患モデルマウスの解析

Publicly Offered Research

Project AreaGeneration of synapse-neurocircuit pathology
Project/Area Number 25110707
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGunma University

Principal Investigator

定方 哲史  群馬大学, 先端科学研究指導者育成ユニット, 助教 (90391961)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
KeywordsCAPS2 / ARF / autism / tremor / trafficking / exocytosis
Outline of Annual Research Achievements

本研究期間において、我々はCAPS2 exon 3 のみがスキップを起こす自閉症モデルマウスを作製した。exon3がスキップした欠損型CAPS2は、シナプス部に輸送されなくなることなどが判明した。また、このマウスが新奇環境への適応不全、社会性行動の異常などの自閉症様の形質を示すことを明らかにした。これらの結果から、欠損型CAPS2の発現によってBDNFの局所的分泌パターンが異常になり、これが自閉症脳における神経ネットワークの形成異常につながる可能性が示唆された。
我々がCAPS2遺伝子と自閉症との関連を最初に報告した後、複数の自閉症患者からCAPS2遺伝子を含む非常に狭い領域が片方の染色体で欠失している例が見つかってきた(Szatmari et al., Nature Genet., 2007; Christian et al., Biol. Psychiatry, 2008)。そこでCAPS2ヘテロマウスの解析を行ったところ、社会性行動の異常や新奇性の高い環境への不適応といった一部の自閉症様行動が見られることが明らかになった。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (10 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (3 results) (of which Invited: 3 results)

  • [Journal Article] Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice.2015

    • Author(s)
      Yuriko Mishima, Yo Shinoda, Tetsushi Sadakata, Masami Kojima, Shigeharu Wakana, Teiichi Furuichi.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 1-6

    • DOI

      10.1038/srep08932

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Age-dependent redistribution and hypersialylation of the central myelin paranodal loop membrane protein Opalin in the mouse brain.2014

    • Author(s)
      Yumi Sato, Fumio Yoshikawa, Tetsushi Sadakata, Yo Shinoda, Michinori Koebis, Teiichi Furuichi.
    • Journal Title

      Neurosci Letter

      Volume: 581 Pages: 14-19

    • DOI

      10.1016/j.neulet.2014.08.017

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum.2014

    • Author(s)
      Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Saruta C, Ishizaki Y, Yuzaki M, Kojima M, Furuichi T.
    • Journal Title

      PLoS One.

      Volume: 9(6) Issue: 6 Pages: 1-10

    • DOI

      10.1371/journal.pone.0099524

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mouse models of mutations and variations in autism spectrum disorder-associated genes : mice expressing caps2/cadps2 copy number and alternative splicing variants2013

    • Author(s)
      Sadakata T, Shinoda Y, Sato A, Iguchi H, Ishii C, Matsuo M, Yamaga R, Furuichi T
    • Journal Title

      Int J Environ Res Public Health

      Volume: 10 Issue: 12 Pages: 6335-6353

    • DOI

      10.3390/ijerph10126335

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain.2013

    • Author(s)
      Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Tanaka M, Iwasato T, Itohara S, Furuyama K, Kawaguchi Y, Ishizaki Y, Yuzaki M, Furuichi T.
    • Journal Title

      J Neurosci.

      Volume: 33 Issue: 44 Pages: 17326-17334

    • DOI

      10.1523/jneurosci.2777-13.2013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Animal Models of Autism Spectrum Disorder (ASD): A Synaptic-Level Approach to Autistic-Like Behavior in Mice2013

    • Author(s)
      Yo Shinoda, Tetsushi Sadakata, Teiichi Furuichi
    • Journal Title

      Experimental Animals.

      Volume: 62 Pages: 71-78

    • NAID

      10031163545

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autistic-like behavioral phenotypes in a mouse model with copy number variation of the CAPS2/CADPS2 gene2013

    • Author(s)
      Sadakata T, Shinoda Y, Oka M, Sekine Y, Furuichi T.
    • Journal Title

      FEBS Lett

      Volume: 587 Issue: 1 Pages: 54-59

    • DOI

      10.1016/j.febslet.2012.10.047

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 有芯小胞分泌不全と自閉症2014

    • Author(s)
      定方哲史
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 自閉症関連遺伝子CAPS22014

    • Author(s)
      定方哲史
    • Organizer
      第61回北関東医学会総会
    • Place of Presentation
      前橋
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 自閉症モデルマウスを用いた発症メカニズムの解明2013

    • Author(s)
      定方哲史
    • Organizer
      平成25年度生理学研究所研究会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-15   Modified: 2019-07-29  

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