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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在初步实验中，我们已经确定在内分泌室外过度表达EP-CAM转基因会导致大的胰岛。这个项目的目标是测试转基因过表达的EP-CAM在小鼠成年胰腺祖细胞中的表达，通过Sox9的表达来确定是否导致这个细胞池的扩大，并促进新的β细胞的发育。利用双基因转基因系统，我们的计划是激活EP-CAM在Sox9成体导管细胞室中的过度表达。在第二系列实验中，我们还将使用四半胱氨酸标记的EP-CAM结构(HEP-CAM-TC)来产生转基因小鼠。产生该品系转基因基因的基本原理是能够在体外和体内对细胞-细胞连接进行相关的光学/电子显微镜形态计量学研究，遵循美国国立卫生研究院(UCSD)最近开发的相关显微技术。

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).