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Functional analysis of Cdk5 by using conditional KO of its activating subunit p35

Research Project

Project/Area Number 21500356
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionWaseda University

Principal Investigator

OHSHIMA Toshio  早稲田大学, 理工学術院, 教授 (20311334)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsキナーゼ / リン酸化 / コンディショナルKO
Research Abstract

The purpose of this study is to analyze the function of neuron-specific serine/threonine kinase Cyclin-dependent kinase 5(Cdk5) by using conditional KO mice of its activating subunit p35 trough the behavioral analysis such as spatial learning and fear conditioning test, and electrophysiological analysis and biochemical analysis. In this study we generated p35-flox mice in which two loxP sequences were inserted in p35 gene allele. We generated inducible p35 conditional KO by crossing p35-flox and CreER mice in which Cre is activated by Tamoxifen(TM) and p35 gene was destructed after brain formed. We confirmed decrease of p35 protein by p. o. administration of 2 mg TM for three days. We also generated CA1-specific p35 conditional KO mice by crossing CaMKII-Cre mice, and confirmed decreased level of p35 protein in hippocampus. We observed decreased numbers of dendritic spines in the hippocampal CA1 pyramidal neurons in CA1-p35 cKO mice. Using these p35 conditional KO mice, we currently conduct behavioral analysis of p35 cKO mice.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (14 results)

All 2012 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (4 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Phosphorylation of CRMP2 is involved in proper dendritic field organization2012

    • Author(s)
      Yamashita N, Ohshima T, Nakamura F, Kolattukudy P, Honnorat J, Mikoshiba K, Goshima Y
    • Journal Title

      J. Neurosci

      Volume: 32 Pages: 1360-1365

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of CRMP2 is involved in proper dendritic field organization2012

    • Author(s)
      Yamashita N, Ohshima T, Goshima Y., et al
    • Journal Title

      J.Neurosci.

      Volume: 32 Pages: 1360-1365

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypomyelination Phenotype Caused by Impaired Differentiation of Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice2011

    • Author(s)
      He X, Takahashi S, Suzuki H, Hashikawa, T, Kulkarni AB, Mikoshiba K, Ohshima T
    • Journal Title

      Neurochem Res

      Volume: 36 Pages: 1293-1303

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emxlcre mediated Cdk5 conditional knockout mice2011

    • Author(s)
      He X, Takahashi S, Ohshima T., et al
    • Journal Title

      Neurochem Res

      Volume: 36 Pages: 1293-1303

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation2010

    • Author(s)
      Tsutsumi K, Takano T, Endo R, Fukuda M, Ohshima T, Tomomura M, Hisanaga S
    • Journal Title

      PLoS ONE

      Volume: 5(4)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration2009

    • Author(s)
      Takahashi S, Ohshima T, Hirasawa M, Pareek TK, Bugge TH, Morozov A, Fujieda K, Brady RO, Kulkarni AB
    • Journal Title

      American J. Pathology

      Volume: 176 Pages: 320-329

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice2009

    • Author(s)
      Nakamura F, Ugajin K, Yamashita N, Okada T, Uchida Y, Taniguchi M, Ohshima T, Goshima Y
    • Journal Title

      J. Comp. Neurol

      Volume: 516 Pages: 360-375

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Commitment of 1-methyl-4-phenylpyrinidinium ion-induced neuronal cell death by proteasome-mediated degradation of p35 Cyclin-dependent kinase 5 activator2009

    • Author(s)
      Endo R, Saito T, Asada A, Kawahara H, Ohshima T, Hisanaga S
    • Journal Title

      J. Biol. Chem

      Volume: 284 Pages: 26029-39

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] Collapsin response mediator proteins regulate bifurcation of apical dendrites in hippocampal CA1 pyramidal neurons during the brain development2011

    • Author(s)
      Niisato E, Nagai, J, Yamashita N, Nakamura F, Goshima Y, and Ohshima T
    • Organizer
      2011 SFN annual meeting
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-13
    • Related Report
      2011 Final Research Report
  • [Presentation] Hypomyelination Phenotype Caused by Impaired Differentiation of Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice.2010

    • Author(s)
      He X, et al.
    • Organizer
      BMB 2010
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice2010

    • Author(s)
      He X, Takahashi S, Suzuki H, Hashikawa T, Kulkarni AB, Mikoshiba K, Ohshima T
    • Organizer
      BMB 2010
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of collapsin response mediator proteins for dendritic development in hippocampal CA1 pyramidal neurons2010

    • Author(s)
      Niisato E, Yamashita N, Nakamura F, Goshima Y, Ohshima T
    • Organizer
      Neuro 2010
    • Related Report
      2011 Final Research Report
  • [Book] 神経特異的キナーゼCdk5の神経発達と神経変性への関与. Brain Science Review 20102010

    • Author(s)
      大島登志男
    • Publisher
      クバプロ
    • Related Report
      2011 Final Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.ohshima.biomed.sci.waseda.ac.jp/

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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