上皮细胞连接分子EpCAM是肿瘤生物学和干细胞生物学研究的热点，已被证明具有多种生物学功能。申请者发现，在敲除EpCAM基因的条件下，新生小鼠肠上皮细胞间的紧密连接结构和功能受到明显影响，出生后10天内死亡。因此，EpCAM基因对成年鼠肠上皮细胞间各种连接结构（紧密连接、粘附连接、桥粒连接等）的作用尚不知晓。上皮细胞的极性对细胞间连接具有依赖性已成共识。EpCAM可能通过调节肠细胞间连接来影响肠细胞极性，进而维持肠上皮组织的稳定性。本项目拟制作条件性EpCAM基因打靶小鼠，通过分别与Rosa26-Cre ERT2或Villin-Cre ERT2小鼠杂交在成年小鼠的全身或肠上皮组织中特异性敲除EpCAM基因，分析EpCAM与肠上皮细胞间各种细胞连接分子的作用关系及EpCAM对肠上皮细胞极性的调节作用。为EpCAM在干细胞和多种上皮组织起源的肿瘤组织中的作用机制的研究提供重要参考。

EpCAM (CD326, also known as Tacstd1), a type I transmembrane glycoprotein that is highly expressed in many rapidly growing tumors of epithelial origin, embryonic and somatic stem cells is implicated in various biological events. We have generated EpCAM global knockout mouse models, and have found that the structure and function of tight junctions in the intestinal epithelium of EpCAM mutant mice impaired significantly. We plan to study the molecular mechanism of EpCAM in regulating the junctions and polarity of the intestinal epithelium using EpCAM condational knockout mouse models. This research will contribute to understanding the detailed mechanism of EpCAM in maintaining the homeostasis of epithelial tissues, and it will also provide guidance for prevention and treatment of many types of cancers and other diseases.