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ゲノム工学を用いて作製した自閉症マウスの解析による精神機能の分子的基盤研究

Research Project

Project/Area Number 20023030
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHiroshima University

Principal Investigator

内匠 透  Hiroshima University, 大学院・医歯薬学総合研究科, 教授 (00222092)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2009: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2008: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywords遺伝学 / 行動学 / 神経科学 / ゲノム / 脳神経疾患
Research Abstract

ヒトゲノム計画が達成されたポストゲノム時代においても、脳機能においては、分子とシステムあるいは表現型との距離が今なお遠い。神経疾患においては、かなりの疾患関連遺伝子の単離、分子病態解明が進んだが、精神疾患においては、今なお臨床医学と基礎的脳科学の距離が離れており、アプローチすら困難な状況にある。研究代表者(内匠)は、最新の染色体工学的手法を用いて、ヒトの生物学異常としての染色体異常(インプリンティング領域でもあるヒト染色体15q11-13の重複)をマウスに構築し、精神行動異常(自閉症)の前向き遺伝学のためのファウンダーマウスを人工的に作製することに成功した。本マウスの解析により、ヒトモデルでもある父性重複ヘテロ(patDp/+)マウスには、社会的相互作用の障害、超音波啼鳴におけるコミュニケーション発達障害、常同様行動、ルーチン行動への執着性等の自閉症様行動がみられた。さらに、C57BL6にパッククロスしたマウスを用いて、行動解析を行った結果、既に見られていた行動結果と同様の、3-チャンバーテストにおける社会的相互作用の障害やBarnes迷路や水迷路の逆転学習における固執性等の自閉症様行動が種を超えて観察された。種を超えて自閉症様行動が見られることから、本モデルマウスの行動異常は種に依存したものではなく、重複領域にその原因があることが示唆された。また、本モデルマウスが、ヒト型自閉症モデルマウスとして有効であることを示している。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (19 results)

All 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (7 results)

  • [Journal Article] Fezfl is required for penetration of the basal lamina by olfactory axons to promote olfactory development.2009

    • Author(s)
      Y.Watanabe, K.Inoue, A.Okuyama-Yamarnoto, N.Nakai, J.Nakatani, K.-i.Nibu, N.Sato, Y.Iiboshi, K.Yusa, G.Kondoh, J.Takeda, T.Terashima T.Takumi
    • Journal Title

      J.Comp.Neurol. 515

      Pages: 565-584

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abnormal behavior in a chromosome-engineering mouse model for human 15q11-13 duplication seen in autism.2009

    • Author(s)
      J.Nakatani, K.Tamada, F.Hatanaka, S.Ise, H.Ohta, K.Inoue, S.Tomonaga, Y.Watanabe, Y.J.Chung, R.Banerjee, K.Iwamoto, T.Kato, M.Okazawa, K.Yamauchi, K.Tanda, K.Takao, T.Miyakawa, A.Bradley, T.Takumi
    • Journal Title

      Cell 137

      Pages: 1235-1246

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The resetting of the circadian rhythm by Prostaglandin J2 is distinctly phase-dependent2009

    • Author(s)
      Koinuma, S., Yagita, K., Fujioka, A., Takashima, N., Takumi, T. and Shigeyoshi, Y.
    • Journal Title

      FEBS Lett 583

      Pages: 413-418

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TLS interaction with NMDA R1 splice variant and Myosin Va in retinal ganglion cell line RGC-52009

    • Author(s)
      Selamat, W. B., Wang, Y., Jamari, I., Takumi, T., Wong, F. and Fujii, R.
    • Journal Title

      Neurosci. Lett. 450

      Pages: 163-166

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TLS-GFP cannot rescue mRNP formation near spines and spine phenotype in TLS-KO2009

    • Author(s)
      Fujii, R., Grossenbacher-Zinchuk, O., Jamari, I., Wang, Y., Zinchuck, V. and Takumi. T.
    • Journal Title

      NeuroReport 20

      Pages: 57-61

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comment on Differential rescue of light-and food-entrainable circadian rhythms2008

    • Author(s)
      Mistlberger, R. E., Yamazaki, S., Pendergas, J. S., Landry, G. J., Takumi, T. and Nakamura. W.
    • Journal Title

      Science 322

      Pages: 675-675

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Of mice and men-universality and breakdown of behavioral organization2008

    • Author(s)
      Nakamura, T., Takumi, T., Takano, A., Aoyagi, N., Yoshiuchi, K., Struzik, Z. R. and Yamamoto, Y.
    • Journal Title

      PLoS ONE 3

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo real-time monitoring of circadian timing in freely moving mice2008

    • Author(s)
      Nakamura, W., Yamazaki, S., Nakamura, T. J, Shirakawa, T., Block, G. D. and Takumi, T.
    • Journal Title

      Corr. Biol. 18

      Pages: 381-385

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes2008

    • Author(s)
      Nakahata, Y., Yoshida, M., Takano, A., Soma, H., Yamamoto, T., Yasuda, A, Nakatsu, T. and Takumi, T.
    • Journal Title

      BMC Mol. Biol. 9

      Pages: 1-1

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/R or2 signaling.

    • Author(s)
      M.Enomoto, S.Hayakawa, D.Ren, S.Itsukushima, M.Matsuo, K.Tamada, C.Oneyama, M.Okada, T.Takumi, M.Nishita, Y.Minami
    • Journal Title

      Oncogene (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fezfl is required for penetration of the basal lamina by olfactory axons to promote olfactory development

    • Author(s)
      Watanabe, Y., Inoue, K., Okuyama-Yamamoto, A., Nakai, N., Nakatani, J., Nibu, K., Sato, N., Iiboshi, Y, Yusa, K., Kondo, G., Takeda, J., Terashima, T. and Takumi, T.
    • Journal Title

      J. Cornp. Neurol. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Robust food anticipatory activity in BMAL 1-deficient mice

    • Author(s)
      Pendergas, J. S., Nakamura, W., Friday, R. C., Hatanaka, F., Takumi, T. and Yamazaki, S.
    • Journal Title

      PLoS ONE (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 染色体工学的手法によるヒト染色体15 q 11-13重複モデルマウスの作製2009

    • Author(s)
      畠中史幸・内匠透
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] A molecular approach towards an understanding of mind and behavior2008

    • Author(s)
      Toru Takumi
    • Organizer
      BMB2008
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] Biolozical Clock2008

    • Author(s)
      Toru Takumi
    • Organizer
      5^<th> Japanese-German Frontier of Science Symposium
    • Place of Presentation
      Germany, Maintz
    • Year and Date
      2008-11-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular mechanisum of the biological clock and its output in circadian physiology and pathophysiology2008

    • Author(s)
      Toru Takumi
    • Organizer
      11^<th> World Congress on Psychiatric Genetics
    • Place of Presentation
      Osaka International Convention Center
    • Year and Date
      2008-10-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] 自閉症前向き遺伝学のためのヒト染色体異常モデルマウスの作製2008

    • Author(s)
      内匠透
    • Organizer
      日本人類遺伝学会第53回大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-09-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 発達障害の動物モデル作製と創薬に向けて2008

    • Author(s)
      内匠透
    • Organizer
      第10回科学技術交流フォーラム
    • Place of Presentation
      東京大学
    • Year and Date
      2008-06-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 染色体工学的手法によるヒト染色体15q11-13重複モデルマウスの作製2008

    • Author(s)
      内匠透
    • Organizer
      第50回日本小児神経学会総会第50回総会国際小児神経シンポジウム
    • Place of Presentation
      第50回日本小児神経学会総会第50回総会国際小児神経シンポジウム
    • Year and Date
      2008-05-30
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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