The pathophysiological analysis for histamine H2 receptor knockout mice.

组胺H2受体敲除小鼠的病理生理学分析。

• 批准号: 11470135
• 负责人: SUGANO Kentaro
• 金额: $ 9.15万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470135/
• 关键词: Histamine H2 receptor; knockout mice; transgenic mice; ヒスタミンH_2受容体

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.

我们已经报道了使用H2受体特异性抗体，组胺H2受体定位于壁细胞的基底外侧表面。我们成功地通过同源重组产生了H2受体缺陷小鼠。然而，在初步研究中，这些基因敲除小鼠的胃粘膜结构与正常对照小鼠基本相似。这些小鼠的酸分泌虽然通过胆碱能途径保存，但并不像预期的那样依赖于组胺。另一课题组对h2受体敲除小鼠进行了较长时间的观察，发现这些小鼠胃黏膜变得肥厚，可能是胃泌素升高所致。为了进一步阐明组胺H2受体在体内的功能，我们在壁细胞中培养了过表达H2受体的转基因小鼠。这些小鼠由于胃粘膜壁细胞数量的增加而表现出胃粘膜厚度的增加。我们目前正在用免疫组织化学和生化方法分析小鼠的表型。随着这些结果，我们现在正试图分析转基因小鼠模型中负责胃粘膜发育的转录因子。

项目成果

Y.Fukushima, T.Saitoh, E.Saitoh, N.Matsuhashi, K.Sugano: "Different roles of G Protein-coupled Receptor Kinases in Histamine H2 Receptor Desensitization."Therapeutic Research. 21 (suppl.1). S46-S48

Y.Fukushima、T.Saitoh、E.Saitoh、N.Matsuhashi、K.Sugano：“G 蛋白偶联受体激酶在组胺 H2 受体脱敏中的不同作用。”治疗研究。

Sugano K.: "Optimum management of mild esophagitis in Japan."J.Gastroenterol.. 34. 540-541 (1999)

Sugano K.：“日本轻度食管炎的最佳治疗。”J.Gastroenterol.. 34. 540-541 (1999)

福嶋康之,菅野健太郎 他: "ヒスタミンH_2受容体脱感作におけるG Protein-coupled Receptor Kinaseの役割"Therapeutic Research. 21. S46-S48 (2000)

Yasuyuki Fukushima、Kentaro Kanno 等：“G 蛋白偶联受体激酶在组胺 H_2 受体脱敏中的作用”21. S46-S48 (2000)。

菅野健太郎: "ガストリン受容体"臨床消化器内科. vol.15(4). 375-380 (2000)

菅野健太郎：“胃泌素受体”临床胃肠病学第 15 卷（4）（2000 年）。

Y.Konda,K.Sugano et al: "Gastrin simulates the growth of gastric pit with less-differenciated features."Am.J.Physiol.. 277(4Ptl). G7773-G7784 (1999)

Y.Konda、K.Sugano 等人：“胃泌素以低分化特征模拟胃凹的生长。”Am.J.Physiol.. 277(4Ptl)。