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Multidimensional analyses of the CDKL5, a causative gene for neurodevelopment disorders, by proteomic and LOF approaches

Research Project

Project/Area Number 23500381
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neuroscience in general
Research InstitutionThe University of Tokyo

Principal Investigator

Tanaka Teruyuki  東京大学, 医学(系)研究科(研究院), 准教授 (10246647)

Co-Investigator(Kenkyū-buntansha) 天野 睦紀  名古屋大学, 医学(系)研究科(研究院), 准教授 (90304170)
水口 雅  東京大学, 医学(系)研究科(研究院), 教授 (20209753)
Co-Investigator(Renkei-kenkyūsha) KAIBUCHI Kozo  名古屋大学, 大学院医学系研究科, 教授 (00169377)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords発達障害 / てんかん / シナプス / ノックアウトマウス / プロテオーム解析 / キナーゼ / 海馬 / レット症候群 / プロテオーム / 遺伝子改変マウス / 行動解析 / リン酸化 / 相互作用 / 情動障害 / 記憶障害
Outline of Final Research Achievements

The Cyclin-dependent kinase-like 5 (CDKL5) gene encodes for a serine-threonine kinase sharing homology to Mitogen-activated kinases (MAPKs) and Cyclin-dependent kinases (CDKs). Recently, mutations in the CDKL5 gene have been identified in the patients with neurodevelopmental disorders associated with intractable epilepsies. However, neither its molecular functions or pathomechanisms caused by its mutations are largely unknown. Aiming to elucidate these problems, I have taken multidimensional strategies, combining an unbiased interactome approach and a targeted loss-of-function (LOF) approach. For the LOF approach, we have generated the Cdkl5 knockout mouse and identified various neurological abnormalities. For the interactome approach, we performed the yeast two-hybrid screening and proteomic screening, and identified several CDKL5 interacting proteins. The combination of these approaches suggested possible mechanisms of CDKL5 regulating neural functions during development.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (16 results)

All 2013 2012 2011

All Journal Article (1 results) Presentation (15 results) (of which Invited: 2 results)

  • [Journal Article] 小児の難治性てんかんとCDKL52013

    • Author(s)
      田中輝幸、奥田耕助
    • Journal Title

      Clinical Neuroscience

      Volume: 31 Pages: 699-702

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
  • [Presentation] Functional studies of the CDKL5, a causative gene of neurodevelopmental disorder, by interactome screening and loss-of-function analysis2013

    • Author(s)
      Kosuke Okuda, Aya Watanabe, Shizuka Kobayashi, Toshiya Manabe, Keizo Takao, Tsuyoshi Miyakawa, Masahiro Fukaya, Hiroyuki Sakagami, Tomoki Nishioka, Mutsuki Amano, Kozo Kaibuchi, Masashi Mizuguchi, Teruyuki Tanaka
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] West症候群・非典型Rett症候群の原因遺伝子CDKL5のノックアウトマウス作製・解析による病態機序の解明2013

    • Author(s)
      田中輝幸、水口雅
    • Organizer
      第55回日本小児神経学会総会
    • Place of Presentation
      大分市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 難治性てんかん・発達障害原因遺伝子CDKL5の生体内分子機能・病態機序解析2013

    • Author(s)
      田中輝幸、奥田耕助、渡邉紀、小林静香、真鍋俊也、高雄啓三、宮川剛、深谷昌弘、阪上洋行、水口雅
    • Organizer
      第54回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Multidimensional approach to functional analysis of Cyclin-dependent kinase-like 5, the causative gene for atypical Rett syndrome2012

    • Author(s)
      田中輝幸
    • Organizer
      Rett Syndrome Symposium in Fukuoka
    • Place of Presentation
      ホテルオークラ福岡 (福岡県 福岡市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] West症候群・非典型Rett症候群の原因遺伝子CDKL5の多元的アプローチによる分子機能・病態機序解析2012

    • Author(s)
      田中輝幸、水口雅
    • Organizer
      第54回日本小児神経学会総会
    • Place of Presentation
      ロイトン札幌 (北海道 札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 遺伝子改変動物モデルによる神経発達障害研究と今後の展望」 第85回日本産業衛生学会2012

    • Author(s)
      田中輝幸
    • Organizer
      第85回日本産業衛生学会
    • Place of Presentation
      名古屋国際会議場 (愛知県 名古屋市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 発達障害原因遺伝子CDKL5ノックアウトマウスの表現型解析2012

    • Author(s)
      田中輝幸、奥田耕助、渡邉紀、竹本咲希、佐藤天平、上野寛枝、浅原弘嗣、水口雅
    • Organizer
      第53回日本神経病理学会総会学術研究会
    • Place of Presentation
      朱鷺メッセ (新潟県 新潟市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経発達障害原因遺伝子CDKL5ノックアウトマウスの作製と表現型解析2012

    • Author(s)
      田中輝幸、奥田耕助、渡邉紀、竹本咲希、佐藤天平、上野寛枝、浅原弘嗣、水口雅
    • Organizer
      第52回日本先天異常学会学術集会
    • Place of Presentation
      東京女子医科大学 弥生記念講堂 (東京都 新宿区)
    • Related Report
      2012 Research-status Report
  • [Presentation] Multidimensional analyses of the CDKL5, a causetive gene for neurodevelopmental disorders2012

    • Author(s)
      Kosuke Okuda, Aya Watanabe, Saki Takemoto, Hiroe Ueno, Tempei Sato, Hiroshi Asahara, Masashi Mizuguchi, Teruyuki Tanaka
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場 (愛知県 名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Multidimensional analysis of the CDKL5, a causative gene for neurodevelopemental disorders2012

    • Author(s)
      K. Okuda, A. Watanabe, S. Takemoto, M. Mizuguchi, T. Tanaka
    • Organizer
      Annual Meeting of Society for Neuroscience 2012
    • Place of Presentation
      Ernest N. Morial Convention Center (New Orleans, LA, USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] CDKL5の多元的アプローチによる機能解析 (シンポジウム:脳形成障害とオミックス)2011

    • Author(s)
      田中輝幸、奥田耕助、渡邉紀、佐藤天平、上野寛枝、浅原弘嗣、水口雅
    • Organizer
      第52回 日本神経病理学会総会学術研究会(招待講演)
    • Place of Presentation
      京都テルサ(京都府 京都市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 神経発達障害原因遺伝子CDKL5変異マウスの網羅的行動解析2011

    • Author(s)
      田中輝幸
    • Organizer
      2011年度 包括型脳科学研究推進支援ネットワーク 夏のワークショップ(招待講演)
    • Place of Presentation
      神戸国際会議場(兵庫県 神戸市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Identification and Characterization of Interacting Proteins of CDKL5, a Gene Product Responsible for West Syndrome or Atypical Rett Syndrome2011

    • Author(s)
      Kousuke Okuda, Aya Watanabe, Masashi Mizuguchi, Teruyuki Tanaka
    • Organizer
      第34回 日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県 横浜市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Identification and characterization of interacting proteins of Cdkl5, a gene product responsible for West syndrome or atypical Rett syndrome2011

    • Author(s)
      Kousuke Okuda, Aya Watanabe, Saki Takemoto, Masashi Mizuguchi, Teruyuki Tanaka
    • Organizer
      Society for Neuroscience Annual Meeting 2011
    • Place of Presentation
      Walter E Washington Convention Center (ワシントンDC, アメリカ合衆国)
    • Related Report
      2011 Research-status Report
  • [Presentation] 発達障害原因遺伝子の多元的アプローチによる機能解析2011

    • Author(s)
      田中輝幸
    • Organizer
      第23回 産業神経・行動学研究会(招待講演)
    • Place of Presentation
      名古屋大学医学部(愛知県 名古屋市)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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