• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

視交叉上核神経細胞におけるサーカディアンリズムの発現とPAS関連時計遺伝子

Research Project

Project/Area Number 11233201
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

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

Principal Investigator

本間 研一  北海道大学, 大学院・医学研究科, 教授 (40113625)

Co-Investigator(Kenkyū-buntansha) 白川 哲夫  北海道大学, 歯学部附属病院, 助教授 (00187527)
安倍 博  北海道大学, 大学院・医学研究科, 講師 (80201896)
本間 さと  北海道大学, 大学院・医学研究科, 助教授 (20142713)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥52,500,000 (Direct Cost: ¥52,500,000)
Fiscal Year 2002: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2000: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥13,900,000 (Direct Cost: ¥13,900,000)
Keywords時計遺伝子 / 概日リズム / 視交叉上核 / 母子同調 / 細胞間コミュニケーション / 生物発光レポータ / ヒスタミン欠損マウス / DEC1, DEC2 / 生物時計 / ニューロン / 行動リズム / 遺伝子変異動物 / 組織培養 / リズム同調
Research Abstract

1.視交叉上核サーカディアンリズムの発現とPAS関連時計遺伝子の役割
(1)恒常暗で行動リズムが消失するClock変異マウスの視交叉上核神経細胞の電気活動概日リズムを個別に測定し、個々のニューロンではリズムは消失せず、周期が延長していることを明らかにし、行動リズムの消失が細胞間コミュニケーションの不調によるものであることを明らかにした。
(2)ラット生物時計の生後発育と母子同調のメカニズムを、仔ラット視交叉上核に発現する時計遺伝子、Per1とPer2を指標として解析した。その結果、幼弱ラットでは視交叉上核時計遺伝子が光以外の因子の調節を受けること、母ラットの授乳時刻が概日リズム位相の決定に重要であることが明らかになった。
2.PAS関連時計遺伝子産物の代謝回転とフィードバック機構
(1)分泌型および非分泌型ルシフェレースによる遺伝子発現の生物発光レポーターシステムを開発し、2つの異なる遺伝子発現を同時にリアルタイムで計測できることを理論的に確立した。
(2)bHLH型転写調節因子をコードする新規時計遺伝子DEC1,DEC2を発見し、ラット視交叉上核で強く発現し、リズム変動していること、CLOCK/BMAL1によるPer遺伝子の転写促進作用を強く抑制すること、光に反応して転写が亢進することを明らかにした。
3.サーカデイアンリズムの同調に於けるPAS関連時計遺伝子産物の役割
(1)出生後1週間、母ラットを明期の12時間盲目仔ラットから隔離すると、仔ラットの行動リズム、視交叉上核の時計遺伝子発現リズムが逆転することを明らかにし、母子同調に視交叉上核の生物時計が関与していることを明らかにした。
(2)行動量の減少、行動リズムの周期延長がみられるヒスタミン欠損マウスでは、視交叉上核のPer1,2,3発現リズムに変化はないが、大脳皮質や線条体の時計遺伝子リズムの振幅が著しく低下しており、行動リズムとの関係が示唆された。

Report

(4 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] W.Nakamura, et al.: "Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons"Nature Neurosci.. 5. 399-400 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Ohta, et al.: "Effects of nursing mothers on rPer1 and rPer2 circadian expression in the neonatal rat suprachiasmatic nuclei vary with developmental stage"Eur. J. Neurosci.. 15. 1953-1960 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakao, et al.: "A phase dynamic model of human circadian rhythm"J Biol. Rhythm. 17. 476-489 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Honma et al.: "Dec1 and Dec2 are regulators of the mammalian molecular clock"Nature. 419. 841-844 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Ohta, et al.: "Periodic absence of nursing mothers alters circadian clock in newborn rats"Eur. J. Neurosci.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Honma, S.Honma: "Circadian Clock and Multi-oscillation System"Hokkaido University Press. 1-244 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Tanahashi, et al.: "Continuous measurement of targeted promotor activity by a secreted bioluminescence reporter, Vargula hilgendorfii, luciferase"Anal Biochem.. 289. 260-266 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Abe, et al.: "Clock genes expressions in the suprachiasmatic nucleus and other areas of the brain during rhythm splitting in CS mice"Mol.Brain Res.. 87. 92-99 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Suzuki, et al.: "Quantitative trait locus analysis of abnormal circadian period in CS mice"Mammalian Genome. 12. 272-277 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] W.Nakamura, et al.: "Regional pacemakers composed of multiple oscillator neurons in the rat suprachiasmatic nucleus"Europ.J.Neurosci.. 14. 666-674 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Abe, et al.: "Behavioral rhythm splitting in the SC mouse is related to clock gene expressions outside the suprachiasmatic nucleus"Europ.J.Neurosci.. 14. 1121-1128 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Masubuchi, et al.: "Circadian activity rhythm in methamphetamine-treated clock mutant mouse"Europ.J.Neurosci.. 14. 1177-1180 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Honma, S.Honma: "Zeitgebers, Entrainment and Masking of the Circadian System"Hokkaido University Press. 299 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Shinohara, et al.: "Circadian release of excitatory amino acids in the suprachiasmatic nucleus culture is Ca2+-independent."Neurosci.Res.. 36. 245-250 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Ikeda, et al.: "cDNA Cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2 : Its mRNA expression, subcellular distribution, and chromosomal localization."Biochem.Biophys.Res.Comm.. 261. 493-502 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Shirakawa, et al.: "Synchronization of circadian firing rhythms in cultured rat suprachiasmatic nucleus."Europ.J.Neurosci.. 12. 2833-2838 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Masubuchi, et al.: "Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats."Europ.J.Neurosci.. 12. 4206-4214 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Honma, et al.: "Synaptic communication of cellular oscillations in the rat suprachiasmatic neurons."Neurosci.Lett.. 294. 113-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Namihira, et al.: "Circadian pattern, light responsiveness and localization of clock gene, rPer1 and rPer2, expressions in the rat retina."NeuroReport,. 12. 471-475 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe H, et al.: "Clock genes expressions in the suprachiasmatic nucleus and other areas of the brain during rhythm splitting in CS mice."Mol.Brain Res.. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Tanahashi, et al.: "Continuous measurement of targeted promotor activity by a secreted bioluminescence reporter, Vargula hilgendorfii, luciferase."Anal Biochem,. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Suzuki, et al.: "Quantitative trait locus analysis of abnormal circadian period in CS mice."Mammalian Genome,. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Abe: "Phase-dependent induction by light of rat Clock transcription in the suprachiasmatic nucleus"Mol. Brain Res.. 66. 104-110 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Honma and K.Honma: "Light-induced uncoupling of multi-oscillatory cricadain system in a diurnal rodent, chipmunk, Eutamias Asiaticus"Am. J. Physiol.. 276. R1390-R1396 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Namihira: "Daily variation and light responsiveness of mammalian clock gene Clock, and its pertnar gene BMAL1, transcripts in the pineal body and different areas of brain in rats"Neurosci. Lett.. 267. 69-72 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Abe: "Functional diversities of two activity components of circadian rhythm in genetical splitting mice(CS strain)"J Comp Physiol A.. 184. 243-251 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Namihara: "Circadian rhythms and light responsiveness of mammalian clock genes Clock and BMAL1, transcripts in the rat retina"Neurosci. Lett.. 271. 1-4 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Urata: "Melatonin induces γ-glutamiylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells"Free Radical Biology & Medicine. 27. 838-847 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] W.Yu: "Characterization of three splice variants and genomic organization of the mouse BMAL1 gene"Biochem. Biophys. Res. Comm.. 260. 760-767 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Shinohara: "Circadian release of excitatory animo acids in the suprachiasematic nucleus culture is Ca2+independent"Neuroscience Research. 36. 245-250 (2000)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi