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進行性多巣性白質脳症のモデル動物の作製

Research Project

Project/Area Number 15659091
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionHokkaido University

Principal Investigator

澤 洋文  北海道大学, 大学院・医学研究科, 助教授 (30292006)

Co-Investigator(Kenkyū-buntansha) 本山 昇  国立長寿医療センター, 研究所・老年病研究部, 室長 (50277282)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsJc virus / ヌードマウス / siRNA / JC virus / 感染モデルマウス / 脳内接種 / 転写調節因子
Research Abstract

進行性多巣性白質脳症(progressive multifocal leukoencephalopathy : PML)の原因ウイルスであるJC virus(JCV)の感染はその転写調節によって制御される事が予想される。しかしながらJCV感染は人以外の動物には起こらず、このことからPMLのモデル動物は現在存在していない。本研究では現在確実な治療法が確立されていないPMLに対する治療法の開発の礎として、JCV感染細胞脳内接種による感染マウスの作製およびJCVの転写調節因子を脳に発現するトランスジェニックマウスの作製を目的として、本研究を行なった。
その結果(1)JCV感染細胞をヌードマウスの脳内に接種し、JCV感染モデルマウスを作製することに成功した。さらにこのモデルマウスを用いて、in vitroで効果の有ったsiRNAをin vivoで用い、JCV感染細胞の増殖を抑制した。現在この結果をまとめて英文雑誌に投稿する予定である。(2)JCVの感染を制御する因子として、神経系細胞に特異的に発現する転写調節因子を単離する事を目的として、EMSAでJCV感染神経系細胞にのみ認められたbandをカラムを用いて抽出し、転写因子調節複合体の1因子としてCstFを単離した。しかしCstFは種々の細胞に発現を認めていたため、最終的にsubtracted cDNA libraryを用いたyeast two hybrid assayを行い、JCVの感染制御因子を単離することに成功した。現在その因子をoligodendrocyte特異的に発現させうるpromoter下流に発現させ得るベクターを構築し、トランスジェニックマウスに利用する事を計画している。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Book (1 results) Patent(Industrial Property Rights) (2 results) Publications (6 results)

  • [Journal Article] Synthetic double-stranded RNA [poly (I:C)] combined with mucosal vaccine protects against influenza virus infection.2005

    • Author(s)
      Ichinohe T, Watanabe I, Ito S, Moriyama M, Tamura S, Takahashi H, Sawa H, et al.
    • Journal Title

      J Virol 79

      Pages: 2910-2919

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isolation of a monoclonal antibody recognizing a cell-surface molecule as a receptor for JC virus.2005

    • Author(s)
      Henmi C, Sawa H, et al.
    • Journal Title

      Biochem Biophys Res Commun 327

      Pages: 242-251

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition of virus production in JC virus-infected cells by postinfection RNA interference.2004

    • Author(s)
      Orba Y, Sawa H et al.
    • Journal Title

      J Virol 78

      Pages: 7270-7273

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nuclear entry mechanism of the human polyomavirus JC virus like article : role of importins and the nuclear pore complex.2004

    • Author(s)
      Qu Q, Sawa H, et al.
    • Journal Title

      J Biol Chem 279

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Investigation of simian virus 40 large T antigen in 18 autopsied malignant mesothelioma patients in Japan.2004

    • Author(s)
      Jin M, Sawa H, et al.
    • Journal Title

      J Med Virol 74

      Pages: 668-676

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Variable patterns of varicella-zoster virus reactivation in Ramsay Hunt syndrome.2004

    • Author(s)
      Aizawa H, Ohtani F, Furuta Y, Sawa H, et al.
    • Journal Title

      J Med Virol 74

      Pages: 355-360

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Protection against influenza virus infection by intranasal administration of HA vaccine with chitin microparticles as an adjuvant.2004

    • Author(s)
      Hasegawa H, Ichinohe T, Strong P, Watanabe I, Ito S, Tamura S-i, Takahashi H, Sawa H et al.
    • Journal Title

      J Med Virol 75

      Pages: 130-136

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAs.2004

    • Author(s)
      Takahashi H, Sawa H, et al.
    • Journal Title

      Biochem Biophys Res Commun 313

      Pages: 1073-1078

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nucleolin and the packaging signal, Ψ promote the budding of human immunodeficiency virus type-1 (HIV-1).2004

    • Author(s)
      Ueno T, Tokunaga K, Sawa H, et al.
    • Journal Title

      Microbiol Immunol 48

      Pages: 111-118

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel dynamin-associating molecule, formin-binding Protein 17, induces tubular membrane invaginations and participates in endocytosis.2004

    • Author(s)
      Kamioka Y, Fukuhara S, Sawa H, et al.
    • Journal Title

      J Biol Chem 279

      Pages: 40091-40099

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Crk associates with ERM proteins and promotes cell motility toward hyaluronic acid.2004

    • Author(s)
      Tsuda M, Makino Y, Iwahara T, Nishihara H, Sawa H, et al.
    • Journal Title

      J Biol Chem 279

      Pages: 46843-46850

    • Related Report
      2004 Annual Research Report
  • [Journal Article] JC virus (JCV) agnoprotein colocalizes with tubulin.2003

    • Author(s)
      Endo S, Okada Y, Orba Y, Nishihara H, Tanaka S, Nagashima K, Sawa H
    • Journal Title

      J Neurovirol 9(Suppl 1)

      Pages: 10-14

    • Related Report
      2004 Annual Research Report
  • [Book] The JC virus-like particle overlay assay. In Methods in Molecular Biology (Lieberman PM (ed))2004

    • Author(s)
      Sawa H, Komagome R
    • Publisher
      Humana Press, Totowa, NJ
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] JCウイルスの感染を抑制するAgnoproteinに対するsiRNA配列の決定2004

    • Inventor(s)
      大場 靖子, 澤 洋文他
    • Industrial Property Rights Holder
      科学技術振興機構 理事長 沖村 憲樹
    • Industrial Property Number
      2004-153170
    • Filing Date
      2004-05-24
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] JCウイルスのVP-1に対するsiRNA、およびそれを含有してなる医薬組成物2004

    • Inventor(s)
      大場 靖子, 澤 洋文他
    • Industrial Property Rights Holder
      科学技術振興機構 理事長 沖村 憲樹
    • Industrial Property Number
      2004-153243
    • Filing Date
      2004-05-24
    • Related Report
      2004 Annual Research Report
  • [Publications] Shoya Y, Tokunaga T, Sawa H.et al.: "Human topoisomerase I promotes HIV-1 proviral DNA synthesis"Proc Natl Acad Sci USA. 100. 8442-8447 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogita H, Kunimoto S, Kamioka K, Sawa H, et al.: "EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells."Circ Res. 93. 23-31 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe I, Ross TM, Tamura Si, Ichinohe T, Ito S, Takahashi H, Sawa H, et al.: "Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin."Vaccine. 21. 4532-4538 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohnishi A, Sawa H, et al.: "Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas."J Neuropathol Exp Neurol. 62. 1052-1059 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ricciardiello L, Baglioni M, Giovannini C, Pariali M, Cenacchi G, Ripalti A, Landini MP, Sawa H, et al.: "Induction of Chromosomal Instability in Colonic Cells by the Human Polyomavirus JC Virus."Cancer Res. 63. 7256-7262 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Teramoto T, Kaneko H, Futano M, Sawa H, et al.: "Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia."Scand J Infect Dis. 35. 910-911 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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