Development of histamine H2 receptor-deficient mouse model by gene targeting.

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09470131
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jichi Medical School (1998); The University of Tokyo (1997)
• Principal Investigator: SUGANO Kentaro Jichi Med.Sch., Faculty Medicine, Professor, 医学部, 教授 (60179116)
• Co-Investigator(Kenkyū-buntansha): FUKUSHIMA Yasuhisa Tokyo Unv., Faculty Medicine, Resident, 医学部, 医員
• Project Period (FY): 1997 – 1998
• Keywords: histamine H2 receptor / Gene targeting / 胃酸分泌

Research Abstract

To analyze the functional role of histamine H2 receptors on the physiological regulations not only in gastrointestinal tract but also in whole body including neurological and hematological systems, we tried to develop a mouse model that lacks histamine H2 receptor. As a first step, we cloned mouse histamine H2 receptor gene including non-translated 5' region. With this gene, we constructed a targeting vector that is introduced in ES cells. After selection of ES cells that showed integration of gene targeting segment, these cells are introduced in blastcysts. Several mice in chimeric state were born, but so far no germline transmission was confirmed. Thus, several other ES clones with integration of targeting vectors have been prepared and injected in blastcysts in order to obtain a mouse with germline transmission of the recombinant gene.

Research Products

• [Publications] Fukushima Y, Sugano K et al: "Role of the C terminus in Histamine H2 receptor signaling desensitization and agonist-induced internalization" J.Biol.Chem.272. 19464-19470 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukushima Y.Sugano K et al: "Oligometer formation of histamine H2 receptors expressed in Sf9 and COS7 cells." FEBS lett.409. 283-286 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukushima Y, Sugano K.et al: "Localization of the histamine H2 receptor, a target for anti-ulcer drugs, in gastric parietal cells." Digestin. (in press). (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukushima Y,Asano T,Takata K,Funaki M,Ogihara T,Anai M,TsukudaK,Saitoh T,Katagiri H,Aihara M,Matsuhashi N,Oka Y,Yazaki Y,SuganoK: "Role of the C terminus in Histamine H2 receptor signaling, desensitization, and agonist-induced internalization." J.Biol.Chem.272. 19464-19470 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fukushima Y,Asano T,Saitoh T,Anai M,Funaki M,Ogihara T,Katagiri H,Matsuhashi N,Yazaki Y,Sgano K: "Oligometer formation of histamine H2 receptors expressed in Sf9 and COS7 cells." FEBS lett.409. 283-286 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fukushima Y,Ohmachi Y,Asano T,Nawano M,Funaki M,Anai M,Ogihara T,Inukai K,Onishi Y,Sakoda H,Saitoh T,Matsuhashi N,Yazaki Y,Sugano K: "Localization of the histamine H2 receptor, a target for anti-ulcer drugs, in gastric parietal cells." Digestion. (in press). (1999)
  • Description: 「研究成果報告書概要(欧文)」より