Mechanisms of tight junction dysregulation in the SAMP1/YitFc model of Crohn's disease-like ileitis.

To date, the precise etiology of inflammatory bowel disease (IBD) remains largely unknown; however, it is well accepted that IBD results from a dysregulated mucosal immune response to environmental factors in genetically susceptible hosts. The primary defect, in at least a subpopulation of IBD patients, may be due to abnormal intestinal epithelial barrier function. The SAMP1/YitFc (SAMP) mouse strain is a spontaneous model of IBD, closely resembling Crohn's disease for its histologic features and localization to the terminal ileum. Dysregulated epithelial barrier function that precedes histologic evidence of ileitis has been reported to be the primary defect in SAMP mice. Data suggest that barrier dysfunction occurs in the absence of commensal bacteria and is accompanied by aberrant expression of the tight junction proteins claudin-2 and occludin. Further investigation is needed to define the precise role of the intestinal epithelium, as well as the apical junctional complex and its associated proteins, in the pathogenesis of IBD in order to determine the etiology and aid in the development of novel treatment modalities for these devastating diseases.