GASTRIN AND GROWTH AND DEVELOPMENT

描述（取自申请） 胃泌素是一种肽激素，对酸调节和生长很重要 泌酸粘膜的壁细胞和肠嗜铬样细胞 成人的胃。 胃泌素在发育中的作用 胃肠道并作为胰腺和结肠的生长因子 不太清楚。 最近的研究表明，体外营养作用 胰腺、结肠和成纤维细胞中加工较少的胃泌素形式 即使没有 CC-B/胃泌素受体（唯一已知的受体） 胃泌素受体。 这表明胃泌素可能具有生长因子 缺乏 CC-B/胃泌素受体的组织中的特性，例如 冒号。 我们将使用靶向基因破坏和转基因技术 基因过表达方法以更好地研究胃泌素的体内作用 对胃肠道的生长发育有影响。 我们有 已经创建了胃泌素缺乏的小鼠以及胃泌素过度表达的小鼠 前胃泌素和过度表达甘氨酸延伸的前胃泌素的小鼠。 我们会 通过以下方式分析胃泌素缺陷小鼠的发育异常 组织学和免疫组织化学。 酸调节缺陷将 通过喂养研究进行评估。 对结肠增殖的影响 通过 BrdU 标记评估胃泌素缺乏和胃泌素过度表达情况 老鼠。 最后，胃泌素作为结肠癌生长因子的作用将 使用结肠癌甲基偶氮甲醇模型进行研究 胃泌素缺乏和胃泌素过度表达的小鼠。

DESCRIPTION (taken from application) Gastrin is a peptide hormone important in acid regulation and in the growth of the parietal and enterochromaffin-like cells of the oxyntic mucosa of the adult stomach. The role of gastrin in the development of the gastrointestinal tract and as a growth factor for the pancreas and colon is less clear. Recent studies have shown an in vitro trophic effect of less-processed forms of gastrin on pancreatic, colonic, and fibroblast cell lines, even in the absence of the CC-B/gastrin receptor, the only known gastrin receptor. This suggests that gastrin may have growth factor properties in tissues which lack the CC-B/gastrin receptor, such as the colon. We will use the techniques of targeted gene disruption and the transgenic approach of gene overexpression to better study the in vivo role of gastrin on the growth and development of the gastrointestinal tract. We have already created gastrin deficient mice, as well as mice which overexpress progastrin and mice which overexpress glycine-extended progastrin. We will analyze the gastrin deficient mice for abnormalities in development by histology and immunohistochemistry. Defects in acid regulation will be assessed through feeding studies. Effects on colonic proliferation will be assessed by BrdU labeling in gastrin-deficient, and gastrin over-expressing mice. Finally, the role of gastrin as a growth factor for colon cancer will be studied using the methylazoxymethanol model of colon cancer in the gastrin deficient and gastrin overexpressing mice.