ROLE OF CELL ADHESION MOLECULES IN PANCREATIC ISLET DEVELOPMENT AND FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 在初步的实验中，我们已经确定，转基因过度表达的Ep-CAM外的内分泌隔室的结果在大的胰岛。该项目的目标是测试Ep-CAM在鼠成年胰腺祖细胞中的转基因过表达（通过Sox 9的表达鉴定）是否导致该细胞库的扩增并促进新β细胞的发育。使用双基因转基因系统，我们的计划是激活Ep-CAM过表达，特别是在Sox 9+成人导管细胞室。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）来产生转基因小鼠。产生该系转基因的基本原理是能够在体外和体内进行细胞-细胞连接的相关光学/电子显微镜形态测定研究，遵循NCMIR（UCSD）最近开发的相关显微镜技术。

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).