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The discovery of new physiological effect of histamine by gene-manipulated mice and its application for the creation of pathological model

Research Project

Project/Area Number 10557010
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General pharmacology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

OHTSU Hiroshi  Medicine, Tohoku University, Lecturer, 大学院・医学系研究科, 講師 (60250742)

Co-Investigator(Kenkyū-buntansha) YAMADA Noboru  Kazusa Research Pharm. Center, Mitsubishi-Tokyo Pharm. Co., Lab. Head, かずさ研究所創薬研究所, 主任研究員
ICHIKAWA Atsushi  Pharmacy, Kyoto University, Professor, 大学院・薬学研究科, 教授 (10025695)
WATANABE Takehiko  Medicine, Tohoku University, Professor, 大学院・医学系研究科, 教授 (70028356)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 1999: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥6,600,000 (Direct Cost: ¥6,600,000)
Keywordshistamine / transgenic mouse / histidine decarboxylase / knockout mouse / allergic reaction / behavior / 遺伝子 / レスキュー / 眼電位図 / 行動薬理
Research Abstract

1) We elucidated HDC gene knockout mice. They lack histamine from the whole body ; therefore it is useful for the histamine research.
2) We found several interesting phenotypes including behavior, allergic reaction, and inflammation.
3) For instance, knockout mice showed no extravasation reaction, confirmed by the Evan's blue leakage from the vessel in the immediate-type skin reaction. Moreover, this disappearance of skin reaction was "rescued" by orally supplemented histamine. This shows that the extravasation reaction succeeded after immediate type allergic reaction is controlled by histamine.
4) In the systemic anaphylaxis reaction histamine has been proved to be one of the very important mediators.
5) The activity of the mice during the day and night is also controlled with histamine.
6) Some response to infection was different between wild type and knockout type.
7) It will be high possibility that the mice show different response in tumor infiltration and metastasis. We are planning to irradiate ultraviolet rays or inoculate the cultured cancer cells into the mice and observe the infiltrative and metastatic process.
8) We prepared transgenic mice expressing high histamine in the body. We are going to use these mice for the study of histamine effects on the whole body.

Report

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

    (7 results)

All Other

All Publications (7 results)

  • [Publications] 大津浩: "ミニレビュー「ヒスチジン脱炭素酵素の分子生物学」"生化学. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroshi Ohtsu, mini-review: "Molecular biology of histidine decarboxylase"Seikogaku. April (in press). (2999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大津 浩: "ミニレビュー「ヒスチジン脱炭酸酵素の分子生物学」"生化学. (印刷中)4月号. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuramasu,A.et al.: "Mast coll/basophi1-specific transcriptional regulation of human 1-histidime decarpoxylase gene by CpG methylation in the promcter" Journal of Biological Chemistry. 273. 31607-31614 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueno,H.et al: "Expression of human histidine decarboxylase in Saccharomyus cervisial." J.Biochem.Mol.Biol.Biophys.2. 141-146 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohuchi,Y.et al: "Induction of histidine dicarboxylase in type 2 T helper lymphocytes trated with anti-CD3 antibody" Inflamm Res. 47. S48-S49 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maeda,K.et al: "Induction of 1-histidine decarboxylase in a human mast cell line HMC-1" Exp.Haemato1.26. 325-331 (1998)

    • Related Report
      1998 Annual Research Report

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

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