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Molecular mechanisms of circadian rhythm system and sleep disorders

Research Project

Project/Area Number 10670914
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionSaitama Medical School

Principal Investigator

IKEDA Masaaki  Saitama Medical School, Assistant Prof., 医学部, 講師 (80232198)

Co-Investigator(Kenkyū-buntansha) HONMA Sato  Hokkaido Univ.Medical School, Associate Prof, 医学部, 助教授 (20142713)
ORIMO Akira  Saitama Medical School, Assistant Prof., 医学部, 講師 (70275866)
YOSHIMURA Kazunori  Saitama Medical School, Assistant Prof., 医学部, 助手 (20158497)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordscircadian rhythm / BMAL1 / clock gene / suprachiasmatic nuclei / sleep disorder / BMAL2 / gene analysis / transcription factor / サーカディアンリズム / ヒトゲノム / 細胞内局在 / 睡眠覚醒・リズム障害 / ノックアウト / ヌプライスバリアント
Research Abstract

1) We have cloned a BAC clone for human BMAL1 gene and determined its sequence. It revealed that human BMAL1 coding region consists from 17 exons and several BMAL1 variants are products from splicing variants.
2) We have cloned a BAC clone for mouse BMAL1. Its coding region splits over 30kb.
3) Mouse BMAL1 promoter region was sequenced. We identified the promoter/enhancer region of BMAL1.
4) The transcription start sites for BMAL1 have been identified.
5) Polymorphism of BMAL1 gene from sleep disorders were searched. No polymorphism were identified in the BMAL1 coding region.
6) Two-hybrid system to test the interaction of clock gene products have been established.
7) Luciferase assay system to test the ability to activate mPer1 promoter have been established.
8) Fusion proteins of clock gene have been prepared for examining the interaction of clock gene products.
9) A nobel bHLH-PAS factor have been cloned and designated BMAL2.
10) The expression, chromosomal localization and cellular localization of BMAL2 were examined.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Ikeda,M,Yu,W et al: "cDNA Cloning of a Novel bHLH-PAS Transcription Factor Superfamily Gene, BMAL2 ; Its mRNA Expression, Subcellular Distribution, and Chromosomal Localizatio. "Biochem Biophys Res Commun. 275. 493-502 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masubuchi S,Honma S et al: "Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats "Eur J of Neurosci. 12. 4206-4214 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe H,Honma S et al: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol.Brain Res. 87(1). 92-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 池田正明: "体内時計は転写因子で刻まれる?"バイオサイエンスとインダストリー. 58. 16-21 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 池田正明: "-生物時計関連遺伝子-PASドメインとPAS因子-PAS因子は環境適応素子として生まれた-"日本時間生物学会会誌. 6. 12-25 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 池田正明: "BMAL1と生体リズム"日本神経精神薬理学雑誌(印刷中). 20. 189-198 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda, M, Yu, W, Hirai, M, Ebisawa, T, Honma, S, Yoshimura, K, Honma K, and Nomura M: "cDNA Cloning of a Novel bHLH-PAS Transcription Factor Superfamily Gene, BMAL2 ; Its mRNA Expression, Subcellular Distribution, and Chromosomal Localization"Biochem Biophys Res Commun. 275. 493-502 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masubuchi S, Honma S, Abe H, Ishizaki K, Namihira M, Ikeda M, and Honma K: "Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats"Eur J of Neurosci. 12. 4206-4214 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe H, Honma S, Namihira M, Masubuchi S, Ikeda M, Ebihara S, and Honma K: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol.Brain Res.. 87. 92-99 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaaki Ikeda: "Circadian timekeeping is generated by transcription factors"Bioscience and Bioindustry. 58 (in Japanese). 242-247 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaaki Ikeda: "PAS domain and PAS factors- an aspecto of PAS factors as modules for adaptation to embironment"Japanese Society for Chronobiology. 6 (in Japanese). 12-25 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaaki Ikeda: "BMAL1 and circadian rhythm"Jpn J Neuropsychopharmacol. 20 (in Japanese). 189-198 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda,M,Yu,W et al: "cDNA Cloning of a Novel bHLH-PAS Transcription Factor Superfamily Gene, BMAL2; Its mRNA Expression, Subcellular Distribution, and Chromosomal Localizatio."Biochem Biophys Res Commun. 275. 493-502 (2000)

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

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe H,Honma S et al: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol.Brain Res. 87(1). 92-99 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 池田正明: "体内時計は転写因子で刻まれる?"バイオサイエンスとインダストリー. 58. 16-21 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 池田正明: "-生物時計関連遺伝子-PASドメインとPAS因子-PAS因子は環境適応素子として生まれた-"日本時間生物学会会誌. 6. 12-25 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 池田正明: "BMAL1と生体リズム"日本神経精神薬理学雑誌. (印刷中)20. 189-198 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe H,Honma S et al: "Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus"Mol Blain Res. 66. 104-110 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Namihira M,Honma S et al: "Daily variation and light responsiveness of mammalian clock gene,Clock and 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] Yu, W, Ikeda M et al: "Characterization of three splice variants and genomic organization of the mouse BMAL1 gene."Biochem. Biophys. Res. Commun. 260. 760-767 (1999)

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

    • Related Report
      1999 Annual Research Report
  • [Publications] Ebisawa T, Kajimura N et al: "Alleic Variants of Human Melatonin 1a Receptor: Functionand Prevalence in Subjects with Circadian Rhythm Sleep Disorders"Biochem Biophys Res Commun. 262. 832-837 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ebisawa T, Uchiyama M et al: "Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders"Neurosci Lett,. 280. 29-32 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honma,S.,Ikeda,M.et al: "Circadian oscillation of BMAL1,a parthner of a mammalian clock gene Clock,in rat suprachiasmatic nucleus." Biochem.Biophys.Res.Commun.250(1). 83-87 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe,H.,Honma,S.et al: "Circadian rhythm and light responsiveness of BMAL1 expression,a mammalian clock gene,in the suprachiasmatic nucleus of rats." Neurosci.Lett.258(2). 93-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe H,Honma S.et al: "Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus." Mol Brain Res.in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] 編者:海老原史樹文・深田吉孝、分担著者:池田正明: "生物時計の分子生物学 哺乳類の時計遺伝子" シュプリンガー・フェアラーク東京, 67-79 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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