ROLE OF CELL ADHESION MOLECULES IN PANCREATIC ISLET DEVELOPMENT AND FUNCTION

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在初步实验中，我们已经确定内分泌区外 Ep-CAM 的转基因过度表达会产生大的胰岛。该项目的目标是测试小鼠成年胰腺祖细胞中 Ep-CAM 的转基因过度表达（通过 Sox9 的表达来鉴定）是否会导致该细胞池的扩张并促进新 β 细胞的发育。我们的计划是使用双基因转基因系统，特别是在 Sox9 成体导管细胞区室中激活 Ep-CAM 过度表达。在第二系列实验中，我们还将使用四半胱氨酸标记的 Ep-CAM 构建体 (hEp-CAM-TC) 来生成转基因小鼠。产生该系转基因的基本原理是能够遵循 NCMIR (UCSD) 最近开发的相关显微技术，在体外和体内对细胞-细胞连接进行相关光学/电子显微镜形态测量研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In preliminary experiments we have determined that transgenic over-expression of Ep-CAM outside the endocrine compartment results in large islets. The goal of this project is to test whether transgenic over-expression of Ep-CAM in murine adult pancreatic progenitors, identified by the expression of Sox9, leads to the expansion of this cellular pool and fosters the development of new beta-cells. Using a bigenic transgenic system, our plan is to activate Ep-CAM over-expression specifically in the Sox9+ adult ductal cell compartment. In a second series of experiments we will also use a tetracysteine-tagged Ep-CAM construct (hEp-CAM-TC) to generate transgenic mice. The rationale for generating this line transgenics is to be able to perform correlative optical/electron microscopy morphometric studies of cell-cell junctions, both in vitro and in vivo, following correlative microscopic technologies recently developed at the NCMIR (UCSD).