2002 Fiscal Year Annual Research Report

ヒスチジン脱炭酸酵素遺伝子改変マウスを用いたヒスタミンの機能解析

Research Project

Project/Area Number	13470018
Research Institution	Tohoku University
Principal Investigator	大津浩東北大学, 大学院・医学系研究科, 助教授 (60250742)
Co-Investigator(Kenkyū-buntansha)	桜井映子東北大学, 大学院・医学系研究科, 教務職員照井正東北大学, 大学院・医学系研究科, 助教授 (30172109) 平澤典保東北大学, 大学院・薬学研究科, 助教授 (80181155) 谷内一彦東北大学, 大学院・医学系研究科, 教授 (50192787) 倉増敦朗東北大学, 大学院・医学系研究科, 助手 (90302091)
Keywords	ヒスタミン / ノックアウトマウス / ヒスチジン脱炭酸酵素 / トランスジェニックマウス / 遺伝子 / 感染 / アレルギー / 行動
Research Abstract	私たちは,ヒスタミンの合成酵素であるヒスチジン脱炭酸酵素(HDC)遺伝子のノックアウト(KO)・マウスおよびHDC高発現マウスを作製し,その解析を行った.以下得られた成果につき説明する. I.HDC-KOマウス a)感染防御:ノックアウトマウスが感染に強いことが判明し,その機構として大腸菌の排除機構がノックアウトマウスで活性化されており,それは,食細胞の遊走能が高まっているためであると考えられた(J Immunol 2002). b)呼吸循環:マウスを卵白アルブミンで感作後,吸入にてアレルギー反応を誘発する.その結果起きてくる好酸球増多は,ヒスタミンが無いと起きてこないことが判明した(Am J Respir Crit Care Med 2003). c)アレルギー:皮膚における木綿糸に対する肉芽腫はヒスタミンが無いと形成できない.その反応にはVEGFを介する血管新生が重要であることが判明した(J Exp Med 2002). d)行動:睡眠時の脳波のパターンおよび新しい環境に対する反応にヒスタミンの有無は重要であった(J Neurosci 2002). e)ヒスタミントランスポーター:ノックアウトマウスの肥満細胞を使い,ヒスタミンの顆粒内までの輸送について明らかにした(Eur J Immunol 2002)., II.HDC-TGマウスヒスタミンの高産生マウスを作製して,皮膚の創傷治癒過程について反応を観察した.

Research Products

(13 results)

All Other

All Publications (13 results)

[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)
[Publications] Akira Koarai: "Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness"Am J Respir Crit Care Med. 167. 759-763 (2003)
[Publications] Pap E: "Histidine decarboxylase deficiency in gene knockout mice elevates male sex steroid production"J Endocrinol. 175. 193-199 (2002)
[Publications] Noriyasu Hirasawa: "Enhancement of neutrophil infiltration in histidine decarboxvlase-deficient mice"Immunol. 107. 217-221 (2002)
[Publications] Takehiko Watanabe: "L-Histidine Decarboxylase as a Probe for Studies on Histamine"The Chemical Record. 2. 369-376 (2002)
[Publications] Regis Parmentier: "Anatomical, Physiological and Pharmacological Characteristics of Histidine-decarboxylase Knockout Mice"J Neurosci. 22. 7695-7711 (2002)
[Publications] Yohsio Hori: "Accelerated clearance of E. coli in experimental peritonitis of histamine-deficient mice"J Immunol. 169. 1978-1983 (2002)
[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)
[Publications] Yasuhiko Kubota: "Increased methamphetamine-induced locomotor activity and behavioural sensitization in histamine-deficient mice"J Neurochem. 83. 837-845 (2002)
[Publications] Ohtsu H: "The plasma extravasation induced by dietary supplemented histamine in histamine-free mice"Eur J Immunol. 32. 1698-1708 (2002)
[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)
[Publications] Tanaka S: "Gastric acid secretion in L-histidine decarboxylase deficient mice"Gastroenterol. 122. 145-155 (2002)
[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)

2002 Fiscal Year Annual Research Report

ヒスチジン脱炭酸酵素遺伝子改変マウスを用いたヒスタミンの機能解析

Principal Investigator

大津 浩 東北大学, 大学院・医学系研究科, 助教授 (60250742)

Research Products

[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)

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

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

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

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

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

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

[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)

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

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

[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)

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

[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)

大津浩東北大学, 大学院・医学系研究科, 助教授 (60250742)