The pathophysiological analysis for histamine H2 receptor knockout mice.

我们曾报道，组胺H2受体定位于基底外侧表面的壁细胞，使用H2受体特异性抗体。我们已经成功地产生H2受体缺陷小鼠的同源重组。然而，在初步研究中，这些基因敲除小鼠的胃粘膜结构基本上与正常对照小鼠相似。这些小鼠中的酸分泌虽然通过胆碱能途径保留，但不依赖于组胺。根据其他研究小组对H2受体敲除小鼠的较长时间观察，这些小鼠的胃粘膜变得肥大，这可能是由胃泌素升高引起的。为了进一步阐明组胺H2受体在体内的功能，我们已经产生了在壁细胞中过表达H2受体的转基因小鼠。由于壁细胞数量增加，这些小鼠的胃粘膜厚度增加。我们目前正在分析小鼠的表型，同时进行生物化学和生物化学分析。沿着这些结果，我们现在正试图在转基因小鼠模型中分析负责胃粘膜发育的转录因子。

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.