2000 Fiscal Year Final Research Report Summary
The pathophysiological analysis for histamine H2 receptor knockout mice.
| Project/Area Number |
11470135
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SUGANO Kentaro Jichi Med.Sch., Faculty Medicine, Professor, 医学部, 教授 (60179116)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAKURA Yasuhisa Jichi Med.Sch., Faculty Medicine, Assistant Lecturer, 医学部, 助手 (50275682)
SATOH Kiichi Jichi Med.Sch., Faculty Medicine, Senior Lecturer, 医学部, 講師 (50275707)
MUTO Hiroyuki Jichi Med.Sch., Faculty Medicine, Senior Lecturer, 医学部, 講師 (50322392)
ISHINO Yumiko Jichi Med.Sch., Faculty Medicine, Assistant Lecturer, 医学部, 助手 (80275685)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Histamine H2 receptor / knockout mice / transgenic mice |
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| Research Abstract |
We have reported that the histamine H2 receptor is localized on the basolateral surface of the parietal cells, using antibody specific for H2 receptor. We have succeeded in generating H2 receptor deficient mice by homologous recombination. In a preliminary study, however, the gastric mucosal architecture of these knockout mice is essentially similar to that of normal control mice. The acid secretion in these mice, although preserved via cholinergic pathway, is not dependent on histamine as expected. According to the observation by other research group of H2-receptor knockout mice for a longer period, the gastric mucosa of these mice became hypertrophic that may be caused by elevated gastrin. To further clarify the function of histamine H2 receptor in vivo, we have generated transgenic mice over-expressing H2 receptors in the parietal cells. These mice showed increased thickness of the gastric mucosa due to the increased number of parietal cells. We are currently analyzing the phenotype of the mice with immunohistochemically as well as biochemically. Along with these results, we are now trying to analyze the transcription factors responsible for gastric mucosal development in transgenic mouse models.
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[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.: "Locarization of the histamine H(2) receptor, a target for antiulcer drugs, in gastric parietal cells."Digestion. 60. 522-527 (1999)
Description
「研究成果報告書概要(欧文)」より
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