Document Detail

EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins.
MedLine Citation:
PMID:  22819673     Owner:  NLM     Status:  MEDLINE    
Tight junctions (TJs) connect epithelial cells and form a semipermeable barrier that only allows selective passage of ions and solutes across epithelia. Here we show that mice lacking EpCAM, a putative cell adhesion protein frequently overexpressed in human cancers, manifest intestinal barrier defects and die shortly after birth as a result of intestinal erosion. EpCAM was found to be highly expressed in the developing intestinal epithelium of wild-type mice and to localize to cell-cell junctions including TJs. Claudin-7 colocalized with EpCAM at cell-cell junctions, and the two proteins were found to associate with each other. Claudins 2, 3, 7, and 15 were down-regulated in the intestine of EpCAM mutant mice, with claudin-7 being reduced to undetectable levels. TJs in the mutant intestinal epithelium were morphologically abnormal with the network of TJ strands scattered and dispersed. Finally, the barrier function of the intestinal epithelium was impaired in the mutant animals. These results suggest that EpCAM contributes to formation of intestinal barrier by recruiting claudins to cell-cell junctions.
Zili Lei; Takako Maeda; Atsushi Tamura; Tetsuya Nakamura; Yuji Yamazaki; Hidetaka Shiratori; Kenta Yashiro; Sachiko Tsukita; Hiroshi Hamada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-20
Journal Detail:
Title:  Developmental biology     Volume:  371     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-01-25     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  136-45     Citation Subset:  IM    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
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MeSH Terms
Antigens, Neoplasm / genetics,  metabolism*
Cell Adhesion Molecules / genetics,  metabolism*
Claudin-3 / genetics,  metabolism
Claudins / genetics,  metabolism*
Intestinal Mucosa / embryology,  metabolism*
Mice, Knockout
Tight Junctions / metabolism*
Grant Support
G0900105//Medical Research Council; MR/J007625/1//Medical Research Council; PG/11/102/29213//British Heart Foundation
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cell Adhesion Molecules; 0/Claudin-3; 0/Claudins; 0/Cldn2 protein, mouse; 0/Cldn3 protein, mouse; 0/Cldn7 protein, mouse; 0/claudin 15; 0/tumor-associated antigen GA733

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