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Inflammation and disruption of the mucosal architecture in claudin‐7‐deficient mice
Author(s) -
Chen Yan-Hua,
Lu Zhe,
Ding Lei,
Foreman Oded,
Tatum Rodney,
Lu Qun,
Renegar Randall,
Cao Jian
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.1107.2
Subject(s) - claudin , pathology , inflammation , intestinal mucosa , biology , medicine , tight junction , immunology , microbiology and biotechnology
Integrity of the intestinal epithelium is required for nutrition absorption and defense against pathogens. Multiple claudins are expressed along the gastrointestinal tract, but little is known about their functions. We generated claudin‐7‐deficient (Cldn7−/−) mice and examined their intestines by histology, molecular and cellular biology, as well as biochemistry approaches. Cldn7−/− mice died around 9 days after birth and had severe intestinal defects that included mucosal ulcerations, epithelial cell sloughing and terminal bleeding. Intestines of Cldn7−/− mice produced significantly higher levels of cytokines, NF‐kappa B and COX‐2. In addition, deletion of Cldn7 resulted in the striking upregulation of MMP‐3 and MMP‐7 in Cldn7−/− intestines. Electron microscopy analysis showed that intestines of Cldn7−/− mice had intercellular gaps and cell‐matrix loosening. Biotin tracer leakage was observed in the intestinal epithelial cells of Cldn7−/− mice at postnatal day 5. Most importantly, Cldn7 deletion reduced the expression and altered the localization of integrin a2; disrupted the formation of claudin‐7/integrin a2/claudin‐1 complexes that normally form in epithelial basolateral compartments of intestines. Our study reveals a novel function of claudin‐7 in cell‐matrix interactions and presents a new animal model to study the intestinal inflammation and inflammatory bowel disease in humans.