Creating diseases to understand what prevents them: genetic analysis of inflammation in the gastrointestinal tract

Inflammatory bowel diseases (IBD), including both ulcerative colitis and Crohn's disease, are extremely variable in severity and have strong genetic components. In mice, several mutations are known to favor or inhibit intestinal inflammation. But a comprehensive picture of the pathogenesis of IBD cannot be assembled based on the limited information so far available from mouse genetic analyses, nor can human IBD be stringently ascribed to mutations known to be influential in mice. This review highlights recent progress made using mouse models created through a forward genetic approach towards the understanding of genes that normally prevent intestinal inflammation.

► A forward genetics approach revealed genes important for intestinal homeostasis.
► ER stress management and epithelial proliferation are necessary to prevent colitis.
► A mutation affecting Paneth and goblet cell vesicles leads to spontaneous disease.
► A current molecular understanding of intestinal homeostasis is presented.