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Development of a new transgenic mouse model as a platform for the imaging-based drug discovery and development

Research Project

Project/Area Number 16K15201
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionNagoya University

Principal Investigator

Yamada Kiyofumi  名古屋大学, 医学部附属病院, 教授 (30303639)

Co-Investigator(Kenkyū-buntansha) 伊藤 教道  名古屋大学, 医学部附属病院, 特任助教 (30726310)
Co-Investigator(Renkei-kenkyūsha) NAGAI Taku  名古屋大学, 医学部附属病院, 准教授 (10377426)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsイメージング創薬 / Npas4 / トランスジェニックマウス / Homer1a / キンドリング / 動物モデル / 神経科学 / 脳神経疾患
Outline of Final Research Achievements

In 2016, to regulate the expression of target genes in a neuronal activity-dependent manner, we created a new transgenic mice line (NPAS4-tTA mice) in which the expression of tTA gene is regulated under the control of Npas4 promoter. We obtained the double transgenic mice following mating with tet0-ChR2-EYFP transgenic mice as a reporter. The double transgenic mice exhibited a high background expression of EYFP in the brain with or without pentylentetrazole (PTZ) treatment.
In 2017, we prepared cyclic AMP response element (CRE)-luciferase expression system using AAV vector. We observed a significant increase in chemiluminescent after cocaine treatment in vivo in the brain of mice expressing the CRE-luciferase gene. As to the functional analysis of target genes of Npas4, we demonstrated that Npas4-Homer1a signal played a role in the regulation of homeostatic scaling in the hippocampus.

Report

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

    (8 results)

All 2018 2017 2016 Other

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

  • [Journal Article] Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes.2018

    • Author(s)
      A Sobue, N Ito, T Nagai, W Shan, K Hada, Nakajima A, Y Murakami, A Mouri, Y Yamamoto, T Nabeshima, K Saito, K Yamada
    • Journal Title

      Glia

      Volume: 66 Issue: 5 Pages: 1034-52

    • DOI

      10.1002/glia.23299

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Valocin-containing protein (VCP) is a novel IQ motif containing GTPase activating protein 1 (IQGAP1) interacting protein.2017

    • Author(s)
      Itoh, N., Nagai, T,, Watanabe, T., Taki, K., Nabeshima, N., Kaibuchi, K., Yamada, K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 493 Issue: 4 Pages: 1384-1389

    • DOI

      10.1016/j.bbrc.2017.09.159

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a.2017

    • Author(s)
      2.Shan W, Nagai T, Tanaka M, Itoh N, Furukawa-Hibi Y, Nabeshima T, Sokabe M, Yamada K.
    • Journal Title

      J Neurochem.

      Volume: - Issue: 1 Pages: 19-33

    • DOI

      10.1111/jnc.14274

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors.2017

    • Author(s)
      Shin EJ, Dang DK, Tran TV, Tran HQ, Jeong JH, Nah SY, Jang CG, Yamada K, Nabeshima T, Kim HC.
    • Journal Title

      Arch. Pharm. Res.

      Volume: - Issue: 4 Pages: 403-428

    • DOI

      10.1007/s12272-017-0897-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protective potential of the glutathione peroxidase-1 gene in abnormal behaviors induced by phencyclidine in mice.2016

    • Author(s)
      Tran TV, Shin EJ, Jeong JH, Lee JW, Lee Y, Jang CG, Nah SY, Lei XG, Toriumi K, Yamada K, Nabeshima T, Kim HC.
    • Journal Title

      Mol Neurobiol.

      Volume: - Issue: 9 Pages: 7042-7062

    • DOI

      10.1007/s12035-016-0239-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 1.PolyIC model of schizophrenia:a role of IFITM3 in the neurodevelopmental impairment.2017

    • Author(s)
      Kiyofumi Yamada
    • Organizer
      5th Congress Of Asian College of Neuropsychopharmacology, AsCNP2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 11.IFITM3 regulates polyI:C-induced neuronal impairment through RabGDI.2017

    • Author(s)
      Norimichi Itoh, Taku Nagai, Daisuke Ibi, Akira Nakajima, Toshitaka Nabeshima, Kiyofumi Yamada.
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科医療薬学・附属病院薬剤部

    • URL

      http://www.med.nagoya-u.ac.jp/pharmacy/

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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