GASTRIN AND GROWTH AND DEVELOPMENT

描述(取自应用程序) 胃泌素是一种在酸性调节和生长过程中起重要作用的多肽激素。 胃含氧酸粘膜的壁细胞和肠嗜铬细胞 成人的胃。胃泌素在糖尿病的发生发展中的作用 胃肠道和胰腺和结肠的生长因子 不太清楚。最近的研究表明，黄曲霉毒素具有体外营养作用 胰腺、结肠和成纤维细胞上较少加工形式的胃泌素 系，即使在没有CC-B/胃泌素受体的情况下，也是唯一已知的 胃泌素受体。这表明胃泌素可能具有生长因子。 缺乏CC-B/胃泌素受体的组织的特性，如 冒号。 我们将使用靶向基因干扰和转基因技术 基因过表达更好地研究胃泌素在体内的作用 对胃肠道的生长发育有影响。我们有 已经创造了胃泌素缺乏的小鼠，以及过度表达的小鼠 孕激素和过表达甘氨酸延伸孕激素的小鼠。我们会 分析胃泌素缺陷小鼠的发育异常 组织学和免疫组织化学。酸调节的缺陷将是 通过喂养研究进行评估。对结肠增殖的影响将是 BrdU标记对胃泌素缺乏和胃泌素过度表达的评估 老鼠。最后，胃泌素作为结肠癌生长因子的作用将 用甲氧基甲醇结肠癌模型进行研究 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.