GASTRIN AND GROWTH AND DEVELOPMENT

胃泌素与生长发育

• 批准号: 2451825
• 负责人: THEODORE J KOH
• 金额: $ 11.03万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-05 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2451825
• 关键词: carcinoma; cell proliferation; colon neoplasms; diet route /schedule; disease /disorder model; gastric acid; gastrins; gastrointestinal system; gene targeting; genetically modified animals; growth factor; histogenesis; histology; hormone regulation /control mechanism; immunocytochemistry; laboratory mouse; northern blottings; nutrition related tag; secretion

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.

描述（取自应用程序） 胃泌素是一种肽类激素，在胃酸调节和生长中起重要作用。 胃泌酸粘膜的壁细胞和肠嗜铬样细胞 成人胃 促胃液素在胃肠道发育中的作用 胃肠道和作为胰腺和结肠的生长因子， 不太清楚。 最近的研究表明， 胰腺、结肠和成纤维细胞上较少加工形式的胃泌素 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/胃泌素受体的组织中的性质，例如 结肠 我们将使用靶向基因破坏和转基因技术， 更好地研究胃泌素体内作用的基因过表达方法 对胃肠道的生长和发育的影响。 我们有 已经创造了胃泌素缺乏的小鼠，以及过度表达胃泌素的小鼠， 前胃泌素和过表达甘氨酸延伸的前胃泌素的小鼠。 我们将 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 通过喂养研究评估。 对结肠增殖的影响将是 通过BrdU标记评估胃泌素缺乏和胃泌素过度表达 小鼠 最后，胃泌素作为结肠癌生长因子的作用将 使用结肠癌的甲基偶氮甲醇模型进行研究， 胃泌素缺乏和胃泌素过表达小鼠。