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Analysis of mTOR signaling in central nervous systems

Research Project

Project/Area Number 15K06701
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurophysiology / General neuroscience
Research InstitutionThe University of Tokyo

Principal Investigator

Kassai Hidetoshi  東京大学, 大学院医学系研究科(医学部), 准教授 (40403232)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsmTOR / トランスジェニックマウス / 小脳 / 遺伝子操作マウス / 小脳プルキンエ細胞 / マウス
Outline of Final Research Achievements

We aimed to examine mTOR functions in cerebellar Purkinje cells (PCs) by establishing a mouse model of chronically activated mTOR pathway in PCs. Using constitutively active mTOR, we established double transgenic mice line, in which active mTOR mutant is expressed specifically in PCs (L7-mTOR Tg mice). Immunohistochemical analysis showed that PCs of L7-mTOR Tg mice were remarkably hypertrophied and significantly decreased in their number at 4 weeks of age. Molecularly, L7-mTOR Tg PCs were immunopositive for cleaved caspase 3 and HIF-1alpha, suggesting that PC loss by mTORC1 activation may be caused by apoptotic cell death via hypoxic stress signaling. Behavioral analyses revealed that L7-mTOR Tg mice displayed impaired motor coordination, but normal social behavior. Together, these results indicate that mTORC1 signaling is essential for PC survival and cerebellar functions.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury.2018

    • Author(s)
      Kurano M, Tsuneyama K, Morimoto Y, Shimizu T, Jona M, Kassai H, Nakao K, Aiba A, Yatomi Y
    • Journal Title

      Thromb Haemost.

      Volume: 印刷中 Issue: 06 Pages: 1021-1035

    • DOI

      10.1055/s-0038-1641750

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common marmoset (Callithrix jacchus).2018

    • Author(s)
      Ogonuki N, Inoue H, Matoba S, Kurotaki YK, Kassai H, Abe Y, Sasaki E, Aiba A, Ogura A
    • Journal Title

      Mol Reprod Dev

      Volume: - Issue: 5 Pages: 376-386

    • DOI

      10.1002/mrd.22971

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of human methylation arrays for epigenome research in the common marmoset (Callithrix jacchus).2017

    • Author(s)
      Ueda J, Murata Y, Bundo M, Oh-Nishi A, Kassai H, Ikegame T, Zhao Z, Jinde S, Aiba A, Suhara T, Kasai K, Kato T, Iwamoto K
    • Journal Title

      Neuroscience Research

      Volume: in press Pages: 60-65

    • DOI

      10.1016/j.neures.2017.02.005

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dephosphorylated parafibromin is a transcriptional coactivator of the Wnt/Hedgehog/Notch pathways.2016

    • Author(s)
      Kikuchi I, Takahashi-Kanemitsu A, Sakiyama N, Tang C, Tang PJ, Noda S, Nakao K, Kassai H, Sato T, Aiba A, and Hatakeyama M.
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 12887-12887

    • DOI

      10.1038/ncomms12887

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] mTORの活性化変異と疾患発生2016

    • Author(s)
      葛西秀俊、饗場篤、前田達哉
    • Journal Title

      結節性硬化症の診断と治療最前線

      Volume: - Pages: 46-51

    • Related Report
      2016 Research-status Report
  • [Journal Article] Rho GTPase protein Cdc42 is critical for postnatal cartilage development.2016

    • Author(s)
      Nagahama R, Yamada A, Tanaka J, Aizawa R, Suzuki D, Kassai H, Yamamoto M, Mishima K, Aiba A, Maki K, Kamijo R.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 470 Issue: 4 Pages: 813-817

    • DOI

      10.1016/j.bbrc.2016.01.111

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Activation of mTORC1 signaling in cerebellar Purkinje cells causes cell death and hypertrophy of Purkinje cells2017

    • Author(s)
      坂井祐介・葛西秀俊・中山寿子・中尾和貴・前田達哉・橋本浩一・狩野方伸・饗場篤
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activation of mTORC1 signaling in cerebellar Purkinje cells causes cell death and hypertrophy of Purkinje cells2017

    • Author(s)
      坂井祐介・葛西秀俊・中山寿子・中尾和貴・前田達哉・橋本浩一・狩野方伸・饗場篤
    • Organizer
      第40回 日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Genetic manipulation of mTORC1 signaling in mouse cerebellar Purkinje cell2016

    • Author(s)
      Hidetoshi Kassai, Yusuke Sakai, Hisako Nakayama, Tatsuya Maeda, Kouichi Hashimoto, Masanobu Kano, Atsu Aiba
    • Organizer
      46th annual meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 動物/疾患モデルの作製技術・病態解析・評価手法、恒常的活性化型mTOR による精神神経疾患モデルマウスの作製2017

    • Author(s)
      葛西秀俊・坂井祐介・饗場篤
    • Total Pages
      428
    • Publisher
      技術情報協会
    • ISBN
      9784861046650
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科・疾患生命工学センター・動物資源学部門

    • URL

      http://lar.cdbim.m.u-tokyo.ac.jp/index.html

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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