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Altered colonic barrier function and paracellular permeability in Muc2 −/− mice
Author(s) -
Trusevych Elizabeth Hannah,
Hirota Christina,
Moreau France,
Tran Kim,
MacNaughton Wallace,
Meddings Jon,
Chadee Kris
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.275.9
Subject(s) - mucin , paracellular transport , ussing chamber , mucin 2 , tight junction , barrier function , occludin , claudin , chemistry , in vivo , ex vivo , mucus , western blot , intestinal permeability , epithelium , permeability (electromagnetism) , biophysics , microbiology and biotechnology , biology , biochemistry , immunology , in vitro , membrane , gene expression , ecology , genetics , gene
A single layer of epithelial cells connected by tight junctions (TJ) and an overlying layer of Muc2‐containing mucus serve as the intestinal mucosal barrier. In this study, we investigated whether mice lacking Muc2 mucin ( Muc2 −/− ) have a compromised epithelial barrier, increasing their susceptibility to intestinal inflammation. Full thickness colonic tissues from Muc2 −/− and Wt mice were mounted in Ussing chambers to access ion transport, transepithelial resistance (TER) and mucosal to serosal flux of FITC‐dextran. TJ proteins were analyzed by Western blot and qPCR. Site‐specific and temporal permeability alterations were measured in vivo using oligosaccharide probes. Ussing chamber studies revealed Muc2 −/− mice had increased colonic TER and decreased FITC‐dextran flux when compared to Wt mice, indicating increased barrier function. Of the TJ proteins tested, both barrier‐forming occludin and cation‐selective claudin‐2 protein levels were increased in Muc2 −/− colons. However, in vivo oligosaccharide uptake revealed that Muc2 −/− mice had increased colonic permeability. Surprisingly, colonic epithelial barrier functions were enhanced in the absence of Muc2 mucin, but in vivo measurements show alterations in colonic permeability that were not identified using ex vivo techniques. These studies suggest that Muc2 mucin confers both luminal and epithelial barrier functions. Support: CIHR, CCFC, AIHS