Impaired intestinal barrier function is thought to be a common major factor in food hypersensitivity, inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and colitis-associated cancer (CAC). Joan Heath and colleagues found that Gpa33–/– mice, which do not express the intestinal epithelium-specific cell surface glycoprotein A33 (GPA33), exhibited increased intestinal permeability and hypersensitivity to food antigens. Such alterations worsened upon exposure to dextran sodium sulphate (DSS), an intestinal luminal irritant, and led to the development of colitis in Gpa33–/– mice. Prior administration of azoxymethane (AOM; a colon-specific mutagen) induced CAC in DSS-treated Gpa33–/– mice but not in Gpa33–/– mice treated with AOM alone. Interestingly, human gene expression data showed that GPA33 RNA expression is reduced in the inflamed bowel of CD- and UC-affected individuals. Collectively, these data suggest a role for GPA33 in intestinal barrier function, which influences susceptibility to inflammatory intestinal pathologies. Gpa33–/– mice could be used to test the restoration of barrier function as a strategy to treat and prevent such pathologies. Page 805
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