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Intestinal epithelium specific knockout of nonmuscle myosin II A disrupts epithelial barrier and exaggerates experimental colitis (60.5)
Author(s) -
Naydenov Nayden,
Feygin Alex,
Conti Mary,
Adelstein Robert,
Ivanov Andrei
Publication year - 2014
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.28.1_supplement.60.5
Subject(s) - adherens junction , tight junction , conditional gene knockout , intestinal epithelium , barrier function , colitis , knockout mouse , intestinal mucosa , in vivo , chemistry , epithelium , microbiology and biotechnology , biology , immunology , medicine , cadherin , phenotype , genetics , biochemistry , cell , receptor , gene
The integrity of epithelial monolayers depends on the formation of tight junctions (TJ) and adherens junctions (AJ). TJ and AJ associate with underlying actomyosin bundles that are critical for their stability and function. Our previous in vitro studies have identified nonmuscle myosin II A (NM IIA) as a unique regulator of AJ/TJ structure and barrier properties in the intestinal epithelium. In this study, we investigated the roles of NM IIA in the maintenance of the intestinal epithelial barrier in vivo . Mice carrying a floxed allele of NM IIA were crossed with villin‐cre mice. The progeny demonstrated Mendelian inheritance, suggesting that this NM IIA conditional knockout (cKO) is not embryonically lethal. Immunoblotting indicated that NM IIA expression was specifically ablated solely in the intestinal epithelium, but not in the brain, lung, kidney or liver. NM IIA cKO showed an increased baseline mucosal permeability and exaggerated dextran sodium sulfate (DSS)‐induced breakdown of the intestinal barrier. Furthermore, NM IIA cKO animals demonstrated increased body weight loss, amplified disease activity and epithelial damage during DSS colitis. These findings highlight NM IIA as an important regulator of barrier properties of normal and inflamed intestinal mucosa in vivo . Supported by the Crohn’s and Colitis Foundation of America (NGN) and NIH grants DK083968 and DK084953 to AII . Grant Funding Source : Supported by the Crohn’s and Colitis Foundation of America (NGN) and NIH grants DK083968 and DK08495