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Analysis of the function of DISC1 to understand the pathology of schizophrenia

Research Project

Project/Area Number 19700347
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKeio University

Principal Investigator

KUBO Ken-Ichiro  Keio University, 医学部, 助教 (20348791)

Research Collaborator SAWA Akira  ジョンズホプキンス大学, 精神科, 教授
KAMIYA Atsushi  ジョンズホプキンス大学, 精神科, 講師
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords精神・神経疾患 / 統合失調症 / 双極性感情障害 / 脳の発生 / 大脳皮質 / 海馬 / disrupted in schizophrenia 1 (DISC1) / Bardet-Biedl syndrome / DISC1 / 脳内皮質構造 / 中枢神経系 / 発生 / 精神疾患 / 子宮内電気穿孔法
Research Abstract

スコットランドの精神疾患多発家系の遺伝学的研究で発見されたdisrupted in schizophrenia 1 (DISC1)は、その後の解析の結果、脳の形成に関わる可能性が示唆され、世界的な注目を集めている。本研究では、脳内皮質構造の発生過程において、どのような組織構築の異常がDISC1の機能欠失によって起こるのかを明らかにすることを試みた。DISC1のsiRNA発現ベクターおよび変異体遺伝子発現ベクターを作成し、子宮内電気穿孔法を用いて発生中の中枢神経系に導入した。その結果、DISC1が発生中の大脳皮質興奮性神経細胞のみならず、海馬皮質の発生にも重要な役割を果たしていることが判明した。さらに、DISC1結合分子である、やはり統合失調症および双極性感情障害に連鎖を示すpericentriolar material-1 protein (PCM1)、さらにBardet-Biedl syndromeの原因遺伝子であるBardet-Biedl syndrome-4 protein (BBS4)が、DISC1とともに発生中の大脳皮質形成に重要な役割を持つことを明らかにした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (11 results)

All 2009 2008 2007

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (9 results)

  • [Journal Article] Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.2008

    • Author(s)
      Atsushi Kamiya, Perciliz L. Tan, Ken-ichiro Kubo, Caitlin Engelhard, Koko Ishizuka, Akiharu Kubo, Sachiko Tsukita, Ann E. Pulver, Kazunori Nakajima, Nicola G. Cascella, Nicholas Katsanis, Akira Sawa.
    • Journal Title

      Arch. Gen. Psychiatry 65(9)

      Pages: 996-1006

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4 : a candidate for psychiatric illnesses.2008

    • Author(s)
      Atsushi Kamiya, Perciliz L.Tan, Ken-ichiro Kubo, Caitlin Engelhard, Koko Ishizuka, Akiharu Kubo, Sachiko Tsukita, Ann E.Pulver, Kazunori Nakajima, Nicola G.Cascella, Nicholas Katsanis, Akira Sawa.
    • Journal Title

      Arch.Gen.Psychiatry 65(9)

      Pages: 996-1006

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] The analysis of the role of DISC1 in the cortical neuronal migration2009

    • Author(s)
      Kenji Tomita, Ken-ichiro Kubo, Asuka Uto, Atsushi Kamiya, Akira Sawa, Kazunori Nakajima
    • Organizer
      第38回慶應ニューロサイエンス研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-03-14
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 大脳皮質抑制性神経細胞におけるDISC1の機能解析2008

    • Author(s)
      宇都飛鳥、久保健一郎、金谷繁明、仲嶋一範
    • Organizer
      日本解剖学会関東支部第96回学術集会
    • Place of Presentation
      つくば
    • Year and Date
      2008-11-22
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Genetic disturbance of cortical development: exploring novel animal models for schizophrenia via in utero gene transfer, Society for Neuroscience2008

    • Author(s)
      Atsushi Kamiya, Minae Niwa, Rina Murai, Yukihiro Noda, Ken-ichiro Kubo, Hanna Jaaro-Peled, Saurav Seshadri, Kazunori Nakajima, Toshitaka Nabeshima, Akira Sawa
    • Organizer
      38th Annual Meeting
    • Place of Presentation
      Washington, D.C., U.S. A
    • Related Report
      2008 Final Research Report
  • [Presentation] Transient knockdown of DISC1 in the developing cerebral cortex leads to dopaminergic disturbance and schizophrenia-like deficits in young adult mice2008

    • Author(s)
      Toshitaka Nabeshima, Minae Niwa, Rina Murai, Yukihiro Noda, Ken-ichiro Kubo, Atsushi Kamiya, Hanna Jaaro-Peled, Kazunori Nakajima, Akira Sawa
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] The analysis of the role of DISC1 in the brain layer formation in vivo2008

    • Author(s)
      Kenji Tomita, Ken-ichiro Kubo, Asuka Uto, Atsushi Kamiya, Akira Sawa, Kazunori Nakajima
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Genetic disturbance of cortical development : exploring novel animal models for schizophrenia via in utero gene transfer2008

    • Author(s)
      Atsushi Kamiya, Minae Niwa, Rina Murai, Yukihiro Noda, Ken-ichiro Kubo, Hanna Jaaro-Peled, Saurav Seshadri, Kazunori Nakajima, Toshitaka Nabeshima, Akira Sawa
    • Organizer
      Society for Neuroscience, 38th Annual Meeting
    • Place of Presentation
      Washington, D.C., U.S.A.
    • Related Report
      2008 Annual Research Report
  • [Presentation] The analysis of the role of DISC1 in the neuronal migration of the neocortex in vivo2007

    • Author(s)
      Ken-ichiro Kubo, Atsushi Kamiya, Akira Sawa, and Kazunori Nakajima
    • Organizer
      Society for Neuroscience, 37th Annual Meeting
    • Place of Presentation
      San Diego, CA, U.S.A.
    • Year and Date
      2007-11-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] The analysis of the role of DISC1 in the neuronal migration of the neocortex in vivo2007

    • Author(s)
      Ken-ichiro Kubo, Atsushi Kamiya, Akira Sawa, Kazunori Nakajima
    • Organizer
      Society for Neuroscience, 37th Annual Meeting
    • Place of Presentation
      an Diego, CA, U.S.A.
    • Related Report
      2008 Final Research Report
  • [Presentation] 新皮質の形成においてDISC1が果たす役割の解析2007

    • Author(s)
      久保健一郎、神谷篤、澤明、仲嶋一範
    • Organizer
      第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会合同大会(Neuro2007)
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report 2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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