マウスフリームービング状態での神経核特異的遺伝子発現制御系の開発

• Project/Area Number: 19659072
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Hiroshima University (2008); Osaka Bioscience Institute (2007)
• 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): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2008: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 遺伝学 / 行動学 / 神経科学 / 生理学 / 脳・神経 / 遺伝子

Research Abstract

本申請研究では、既に確立したマウスフリームービング状態での視床下部視交叉上核(suprachiasmatic nucleus, SCN)の電気活動連続記録系(in vivo multiple unit neural activity, in vivo MUA)を発展させ、SCN特異的に遺伝子発現を制御する系を開発することを目的とする。In vivo MUAを用いて、SCNの電気活動の直接の出力が室傍核下部領域であることを示した。すなわち、SCNにおける電気活動の昼間に高い概日リズムは、SPZにおいては、夜に高い位相が逆転した概日リズムを示し、これらの逆位相関係の概日リズムは、分子時計が障害されているClock/Clock変異マウスにおいて、消失することを明らかにした。SPZは、睡眠覚醒、ホルモン分泌や体温調節等、恒常性維持に重要な働きをする視床下部内のいわば解剖学的ハブに位置しており、生物が環境に対して対応していく上(例えば昼行性か夜行性か)で必須な領域と考えられる。また、時計遺伝子プロモーターで制御されるルシフェラーゼモニターマウスを用いて、SCNスライスにおける単一細胞レベルでのリズム発現モニター系を確立した。数理解析の結果、SCN内に3つの位相クラスターが存在することを明らかにした。さらに、In vivo系モニターの検知に必要なCCDカメラの条件検討を行い、記録に必要な環境を得ることができた。

Research Products

• [Journal Article] The resetting of the circadian rhythm by Prostaglandin J2 is distinctly phase-dependent. (2009)
  • Author(s): Koinuma, S., Yagita, K., Fujioka, A., Takashima, N., Takumi, T., Shigeyoshi, Y.
  • Journal Title: FEES Lett 583 Pages: 413-418
  • Peer Reviewed
• [Journal Article] TLS interaction with NMDA R1 splice variant and Myosin Va in retinal ganglion cell line RGC-5. (2009)
  • Author(s): Selamat, W. B., Wang, Y., Jamari, I., Takumi, T., Wong, F., Fujii, R.
  • Journal Title: Neurosci. Lett. 450 Pages: 163-166
  • Peer Reviewed
• [Journal Article] TLS-GFP cannot rescue mRNP formation near spines and spine phenotype in TLS-KO. (2009)
  • Author(s): Fujii, R., Grossenbacher-Zinchuk, O., Jamari, I., Wang, Y., Zinchuck, V., Takumi, T.
  • Journal Title: NeuroRevort 20 Pages: 57-61
  • Peer Reviewed
• [Journal Article] Comment on Differential rescue of light-and food-entrainable circadian rhythms. (2008)
  • Author(s): Mistlberger, R. E., Yamazaki, S., Pendergas, J. S., Landry, G J., Takumi, T., Nakamura, W.
  • Journal Title: Science 322 Pages: 675-675
  • Peer Reviewed
• [Journal Article] Of mice and men-universality and breakdown of behavioral organization. (2008)
  • Author(s): Nakamura, T., Takumi, T., Takano, A., Aoyagi, N., Yoshiuchi, K., Struzik, Z. R., Yamamoto, Y.
  • Journal Title: PLoS ONE 3
  • Peer Reviewed
• [Journal Article] In vivo real-time monitoring of circadian timing in freely moving mice. (2008)
  • Author(s): Nakamura, W., Yamazaki, S., Nakamura, T. J, Shirakawa, T., Block, G. D., Takumi, T.
  • Journal Title: Curr. Biol. 18 Pages: 381-385
  • Peer Reviewed
• [Journal Article] A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes. (2008)
  • Author(s): Nakahata, Y., Yoshida, M., Takano, A., Soma, H., Yamamoto, T., Yasuda, A, Nakatsu, T., ^*Takumi, T.
  • Journal Title: BMC Mol. Biol. 9 Pages: 1-1
  • Peer Reviewed
• [Journal Article] Of mice and men-universality and breakdown of behavioral oraanization (2008)
  • Author(s): Nakamura T
  • Journal Title: PLoS ONE (In press)
  • Peer Reviewed
• [Journal Article] In vivo monitoring of circadian timing in freely moving mice (2008)
  • Author(s): Nakamura W
  • Journal Title: Curr Biol 18 Pages: 381-385
  • Peer Reviewed
• [Journal Article] A direct repeat of E-box-like element is required for cell-autonomous circadian rhythm of clock genes (2008)
  • Author(s): Nakahata Y
  • Journal Title: BMC Mol Biol 9 Pages: 1-1
  • Peer Reviewed
• [Journal Article] 時計遺伝子の転写振動及びその分子メカニズム (2007)
  • Author(s): 内匠 透
  • Journal Title: 自律神経 44 Pages: 246-250
  • NAID: 10019987656
• [Journal Article] リチウムと概日時計とうつ病 (2007)
  • Author(s): 内匠 透
  • Journal Title: Clinical Neuroscience 25 Pages: 1156-1157
• [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., Takumi, T.
  • Journal Title: J. Comp. Neurol. (in press)
  • Peer Reviewed
• [Journal Article] Robust food anticipatory activity in BMAL1-deficient mice.
  • Author(s): Pendergas, J. S., Nakamura, W., Friday, R. C., Hatanaka, F., Takumi, T., Yamazaki, S.
  • Journal Title: PLoS ONE (in press)
  • Peer Reviewed
• [Presentation] 視交叉上核の機能解剖学 (2009)
  • Author(s): 明 智煥, 畠中 史幸, 中村 渉, 内匠 透
  • Organizer: 第114回日本解剖学会総会・全国学術集会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 2009-03-28
• [Presentation] Biological Clock (2008)
  • Author(s): Toru Takumi
  • Organizer: 5^<th> Japanese-German Frontier of Science Symposium
  • Place of Presentation: Germany, Maintz
  • Year and Date: 2008-11-01
• [Presentation] Molecular mechanism of the biological clock and its output in circadian physiology and pathophysiology. (2008)
  • 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
• [Presentation] Molecular Interaction between circadian rhythm and mood disorder. (2008)
  • Author(s): Toru Takumi
  • Organizer: 19^<th> World Congress of the European Sleep Research Society
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2008-09-12
• [Presentation] Molecular chronobiology using whole body (2008)
  • Author(s): Toru Takumi
  • Organizer: 第85回日本生理学会大会シンポジウム「Approach to whole body:New stream to study autonomic nervous and neuroendocrine system
  • Place of Presentation: 東京
• [Presentation] Molecular Mechanism of Circadian Rhythm and Its Clinical Implication (2007)
  • Author(s): Toru Takumi
  • Organizer: The 4th International Joint Symposium of Korea Biomedical Genomic Research Association and Center for Genome Science"Roads to Personalized and Preventive Medicine"
  • Place of Presentation: Seoul,Korea
  • Year and Date: 2007-12-07
• [Presentation] Molecular interaction between depression and circadian beahvior (2007)
  • Author(s): Atsuko Takano
  • Organizer: 2nd World Congress of Chronobiology
  • Place of Presentation: Tokyo
• [Presentation] Rhythmic properties of the mouse suprachiasmatic necleus in vivo (2007)
  • Author(s): Wataru Nakamura
  • Organizer: 2nd World Congress of Chronobiology
  • Place of Presentation: Tokyo
• [Presentation] 生物時計とうつ状態との分子的相関 (2007)
  • Author(s): 高野 敦子
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] in vitroリズムモニター系による時計遺伝子概日転写の分子機構の解明及び同調因子の探索 (2007)
  • Author(s): 松原 千明
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] The blues and rhythm in the body and cells (2007)
  • Author(s): Toru Takumi
  • Organizer: 2nd World Congress of Chronobiology Symposium"Mood disorders and biological clock"
  • Place of Presentation: Tokyo
• [Presentation] Circadian output in the suprachiasmatic nucleus (2007)
  • Author(s): Wataru Nakamura, Toru Takumi
  • Organizer: 日本睡眠学会第32回定期学術集会、第14回日本時間生物学会学術大会シンポジウム「Functional structure of the suprachiasmatic nucleus」
  • Place of Presentation: 東京
• [Presentation] Molecular mechanism of biological clock and its output for circadian physiology and pathophysiology (2007)
  • Author(s): Toru Takumi
  • Organizer: University of Surrey Workshop"Sleep, Circadian Rhythms and Cognition:Bridging the Genotvge-Phenotype Gap"
  • Place of Presentation: Guilford,UK
• [Presentation] 生物時計とうつ状態との分子的相関 (2007)
  • Author(s): 高野 敦子、内匠 透
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会ワークショップ「生物時計分子機構と健康医療」
  • Place of Presentation: 横浜
• [Book] 体内時計はどこにある?-腹?脳?.NPO法人脳の世紀推進会議編 (2007)
  • Author(s): 内匠 透
  • Publisher: クバプロ