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Assessment of function of histamine using histidine decarboxylase gene-manupulated mice

Research Project

Project/Area Number 13470018
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionTohoku University

Principal Investigator

OHTSU Hiroshi (2002)  Tohoku University, Graduate School of Medicine, Pharmacology, Associate Professor, 大学院・医学系研究科, 助教授 (60250742)

渡邉 建彦 (2001)  東北大学, 大学院・医学系研究科, 教授 (70028356)

Co-Investigator(Kenkyū-buntansha) SAKURAI Eiko  Tohoku University, Graduate School of Medicine, Pharmacology, Registrative Staff, 大学院・医学系研究科, 教務職員
TERUI Tadashi  Tohoku University, Graduate School of Medicine, Dermatology, Associate Professor, 大学院・医学系研究科, 助教授 (30172109)
HIRASAWA Noriyasu  Tohoku University, Graduate School of Pharmaceutical Sciences, Laboratory of Pathophysiological Biochemistry, Associate Professor, 大学院・薬学系研究科, 助教授 (80181155)
YANAI Kazuhiko  Tohoku University, Graduate School of Medicine, Pharmacology, Professor, 大学院・医学系研究科, 教授 (50192787)
KURAMASU Atsuo  Tohoku University, Graduate School of Medicine, Pharmacology, Assistant Professor, 大学院・医学系研究科, 助手 (90302091)
桜井 映子  東北大学, 大学院・医学系研究科, 教務職員
大津 浩  東北大学, 大学院・医学系研究科, 助教授 (60250742)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
Keywordshistamine / knockout mice / histidine decarboxylase / transgenic mice / gene / infection / allergy / behavior / 肥満細胞 / 胃酸分泌 / 概日リズム / H2受容体 / SAGE法
Research Abstract

We estimated the role of histamine in the in vivo situation using histidine decarboxylase gene knockout mice generated by us. This gene is expressed in the cells able to produce histamine, which are mast cell, basophil, neron, gastric cell, etc. We clarified the activity of histamine in various allergic diseases, sleep state and secretion of gastric juice. We also newly clarified the relation of histamine to infection and chronic granuloma. For example, in the systemic anaphylaxis reaction, histamine plays a important role for the control of body temperature and respiration, but it does not affect the blood pressure. The knockout mice show electroencepharogram typical for the sleeping wave during waking time. The secretion of gastric juice was induced by gastrin in the wild type mice however it was seased in the knockout mice.The existence of histamine retard the recovery from peritonitis produced by intraperitoneal injection of E..coli. Histamine is important for the chronic granuloma formation triggered with subcutaneous cotton thread implantation. In addition to these in vivo phenotypes we observed intriguing evidence using bone marrow-derived mast cells. Onece we cultured the mast cell in the medium containing histamine, these histamine were absorbed into the secretory granules and could be secreted after the stimulation with lgE and anti-IgE.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Hiroshi Ohtsu: "New Functions of Histamine Found in Histidine Decarboxylase Gene Knockout Mice"Biochem Biophys Res Commun. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zong Chen: "Chemical kindling induced by pentylenetetrazol in histamine H_1 receptor gene knockout mice (H_1KO)"Brain Research. 968. 162-166 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akira Koarai: "Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness"Am J Respir Crit Care Med. 167. 758-763 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Pap E: "Histidine decarboxylase deficiency in gene knockout mice elevates male sex steroid production"J. Endocrinol. 175. 193-199 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noriyasu Hirasawa: "Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice"Immunol. 107. 217-221 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takehiko Watanabe: "L-Histidine Decarboxylase as a Probe for Studies on Histamine"The Chemical Record. 2. 369-376 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Regis Parmentier: "Anatomical, Physiological and Pharmacological Characteristics of Histidine-decarboxylase Knockout Mice:"J. Neurosci.. 22. 7695-7711 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshio Hori: "Accelerated clearance of E. coli in experimental peritonitis of histamine-deficient mice"J. Immunol. 169. 1978-1983 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoko Kobayashi-Makabe: "The control effect of histamine on the body temperature and respiratory function in systemic anaphylaxis"J. Allergy Clin. Immunol. 110. 298-303 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasuhiko Kubota: "Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice"J. Neurochem. 83. 837-845 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtsu H: "The plasma extravasation induced by dietary supplemented histamine in histamine-free mice"Eur. J. Immunol.. 32. 1698-1708 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ghosh, A-K: "Defective angiogenesis in the inflammation granulation tissue in histidine decarboxylase-deficient mice but not mast cell-deficient mice"J. Exp. Med.. 195. 973-982 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka, S: "Gastric acid secretion in L-histidine decarboxylase deficient mice"Gastroenterology. 122. 145-155 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sun, X-M: "Effect of intracellular histamine on the gene expression profile in mouse bone marrow-derived mast cells"Inflamm Res. S1. S11-S12 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtsu, H: "Mice lacking histidine decarboxylase exhibit abnormal mast cells"FEBS Letters. 502. 53-56 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hegyi, K: "Histamine deficiency suppresses murine haptoglobin production and modifies hepatic protein tyrosine"Cell Mol Life Sci. 58. 850-854 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Pallinger E: "Characterization by flow cytometry of hemopoietic progenitors in bone marrow of histidine decarboxylase"Inflamm Res. S12. S89-S90 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wiener Z: "Highly reduced peritoneal mast cell number and decreased c-kit expression in histidine decarboxylase knock out mice"Inflamm Res. S12. S55-S56 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroshi Ohtsu, and Takehiko Watanabe: "New Functions of Histamine Found in Histidine Decarboxylase Gene Knockout Mice"Biochem Biophys Res Commun (Review). in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zong Chen, Zhengyan Li, Eiko Sakurai, Jalal Izadi Mobarakeh, Hiroshi Ohtsu, Takeshi Watanabe, Takehiko Watanabe, Kazuie Iinuma, and Kazuhiko Yanai: "Chemical kindling induced by pentylenetetrazol in histamine H_1 receptor gene knockout mice (H_1KO), histidine decarboxylase-deficient mice (HDC^<-/->) and mast cell-deficient W/Wv mice"Brain Research. 968. 162-166 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akira Koarai, Masakazu Ichinose, Satsuki Ishigaki-Suzuki, Shunsuke Yamagata, Hisatoshi Sugiura, Eiko Sakurai, Yoko Makabe-Kobayashi, Atsuo Kuramasu, Takehiko Watanabe, Kunio Shirato, Toshio Hattori, and Hiroshi Ohtsu: "Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness"Am J Respir Crit Care Med. 167. 758-763 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Pap E, Racz K, Kovacs JK, Varga I, Buza E, Madarasz B, Foldes C, Szalai C, Watanabe T, Ohtsu H, Ichikawa A, Nagy A, Falus A.: "Histidine decarboxylase deficiency in gene knockout mice elevates male sex steroid production"J. Endocrinol.. 175. 193-199 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noriyasu Hirasawa, Hiroshi Ohtsu, Takehiko Watanabe, Kazuo Ohuchi: "Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice"Immunol.. 107. 217-221 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takehiko Watanabe and Hiroshi Ohtsu: "L-Histidine Decarboxylase as a Probe for Studies on Histamine"The Chemical Record. 2. 369-376 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Regis Parmentier, Hiroshi Ohtsu, Zahia Djebbara-Hannas, Jean-Louis Valatx, Takehiko Watanabe and Jian-Sheng Lin: "Anatomical, Physiological and Pharmacological Characteristics of Histidine-decarboxylase Knockout Mice: Evidence for the Role of Brain Histamine in Behavioral and Sleep-wake Control"J. Neurosci.. 22. 7695-7711 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshio Hori, Yoshihiro Nihei, Yoshimochi Kurokawa, Atsuo Kuramasu, Yoko Makabe-Kobayashi, Tadashi Terui, Hideyuki Doi, Susumu Satomi, Eiko Sakurai, Andras Nagy, Takehiko Watanabe, and Hiroshi Ohtsu: "Accelerated clearance of E. coli in experimental peritonitis of histamine-deficient mice"J. Immunol.. 169. 1978-1983 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoko Kobayashi-Makabe, Yoshio Hori, Tetsuya Adachi, Satsuki Ishigaki-Suzuki, Yoshihiro Kikuchi, Yutaka Kagaya, Kunio Shirato, Andras Nagy, Azusa Ujike, Toshiyuki Takai, Takehiko Watanabe and Hiroshi Ohtsu: "The control effect of histamine on the body temperature and respiratory function in systemic anaphylaxis"J. Allergy Clin. Immunol.. 110. 298-303 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasuhiko Kubota, Chihiro Ito, Eiichi Sakurai, Eiko Sakurai, Takehiko Watanabe and Hiroshi Ohtsu: "Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice"J. Neurochem.. 83. 837-845 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtsu,H.; Kuramasu,A.; Tanaka,S.; Terui,T.; Hirasawa,N.; Hara,M.; Makabe-Kobayashi,Y.; Yamada,N.; Yanai,K.; Sakurai,E.; Okada,M.; Ohuchi,K.; Ichikawa,A.; Nagy,A. and Watanabe,T.: "The plasma extravasation induced by dietary supplemented histamine in histamine-free mice"Eur. J. Immunol.. 32. 1698-1708 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ghosh,A-K.; Hirasawa,N.; Ohtsu,H.; Watanabe,T and Ohuchi,K.: "Defective angiogenesis in the inflammation granulation tissue in histidine decarboxylase-deficient mice but not mast cell-deficient mice"J. Exp. Med.. 195(8). 973-982 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka,S.; Hamada,K.; Yamada,N.; Sugita,Y.; Tonai,S.; Hunyady,B.; Palkovits,M.; Falus,A.; Watanabe,T.; Okabe,S.; Ohtsu,H.; Ichikawa, A. and Nagy,A.: "Gastric acid secretion in L-histidine decarboxylase deficient mice"Gastroenterology. 122. 145-155 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sun, X-M.; Kuramasu,A.; Makabe-Kobayashi,Y.; Sakurai,E.; Watanabe,T. and Ohtsu,H.: "Effect of intracellular histamine on the gene expression profile in mouse bone marrow-derived mast cells"Inflamm Res.. S1. S11-12 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtsu,H.; Tanaka,S.; Terui,T.; Hori,Y.; Makabe-Kobayashi,Y.; Pejler,G.; Tchougounova,E.; Hellman,L.; Gertsenstein,M.; Hirasawa,N.; Sakurai,E.; Buzas,E.; Kovacs,P.; Csaba,G.; Kittel,A.; Okada,M.; Hara,M.; Mar,L.; Numayama-Tsuruta,K.; Ishigaki-Suzuki,S.; Ohuchi,K.; Ichikawa,A.; Falus,A.; Watanabe,T. and Nagy,A.: "Mice lacking histidine decarboxylase exhibit abnormal mast cells"FEBS Letters. 502. 53-56 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hegyi,K.; Fulop,A.K.; Toth,S.; Buzas,E.; Watanabe,T.; Ohtsu,H.; Ichikawa,A.; Nagy,A.; and Falus,A.: "Histamine deficiency suppresses murine haptoglobin production and modifies hepatic protein tyrosine phosphorylation"Cell Mol Life Sci. 58. 850-854 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Pallinger E, Buzas E, Laszlo V, Watanabe T, 0htsu H, Ichikawa A, Nagy A, Falus A.: "Characterization by flow cytometry of hemopoietic progenitors in bone marrow of histidine decarboxylase knock out and wild type mice"Inflamm Res. S2. S89-90 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wiener Z, Buzas E, Kovacs P, Csaba G, Szabo D, Kittel A, Pallinger E, Watanabe T, Ohtsu H, Ichikawa A, Nagy A, Falus,A.: "Highly reduced peritoneal mast cell number and decreased c-kit expression in histidine decarboxylase knock out mice"Inflanum Res. Sl 2. S55-56 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zong Chen: "Chemical kindling Induced by pentylenetetrazol in histamine H1 receptor gene knockout mice (H1KO), histidine decarboxylase-deficient mice (HDC-/-) and mast cell-deficient W/Wv mice"Brain Res. 968. 162-166 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akira Koarai: "Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness"Am J Respir Crit Care Med. 167. 759-763 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pap E: "Histidine decarboxylase deficiency in gene knockout mice elevates male sex steroid production"J Endocrinol. 175. 193-199 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noriyasu Hirasawa: "Enhancement of neutrophil infiltration in histidine decarboxvlase-deficient mice"Immunol. 107. 217-221 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takehiko Watanabe: "L-Histidine Decarboxylase as a Probe for Studies on Histamine"The Chemical Record. 2. 369-376 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Regis Parmentier: "Anatomical, Physiological and Pharmacological Characteristics of Histidine-decarboxylase Knockout Mice"J Neurosci. 22. 7695-7711 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yohsio Hori: "Accelerated clearance of E. coli in experimental peritonitis of histamine-deficient mice"J Immunol. 169. 1978-1983 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoko Kobayashi-Makabe: "The control effect of histamine on the body temperature and respiratory function in systemic anaphylaxis"J Allergy Clin Immunol. 110. 298-303 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuhiko Kubota: "Increased methamphetamine-induced locomotor activity and behavioural sensitization in histamine-deficient mice"J Neurochem. 83. 837-845 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsu H: "The plasma extravasation induced by dietary supplemented histamine in histamine-free mice"Eur J Immunol. 32. 1698-1708 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gosh A-K: "Defective angiogenesis in the inflammation granulation tissue in histidine decarboxylase-deficient mice but not mast cell-deficient mice"J Exp Med. 195. 973-982 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka S: "Gastric acid secretion in L-histidine decarboxylase deficient mice"Gastroenterol. 122. 145-155 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sun X-M: "Effect of intracellular histamine on the gene expression profile in mouse bone marrow-derived mast cells"Inflamm Res. S1. S11-S12 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Ohtsu: "Mice lacking histidine decarboxylase exhibit abnormal mast cells"FEBS Letts.. 502. 53-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Tanaka: "Gastric acid secretion in L-hisitidine decarboxylase-deficient mice"Gastroenterology. 122. 145-155 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] X.-M.Sun: "Identification of expressed gene profiles affected by the intracellular histamine in mouse mast cells"Inflam. Res.. 51(Swp, I). S11-S12 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Kuramasu: "Identification of novel mast cell genes by serial analysis of gene expression in cord blood-derived mast cells"FEBS Letts.. 58. 850-854 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Hegy: "Histamine deficiency suppresses murine haptoglobin production and modifies hepatic protein tyrosine phosphorylation"Cell. Mol. Life Sci.. 58. 850-854 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Watanabe: "Studies on functions of the histaminergic neuron system by using pharmacological agents, Knockout mice and PET"Tohoku J. Exp. Med.. 195. 197-217 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Watanabe: "Histamine Research in a New Millennium"Elsevier, Amsterdam. 521 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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