Animal Models of Inflammatory Bowel Disease at the Dawn of the New Genetics Era

Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory intestinal diseases with multifactorial etiologies. CD and UC are distinguished both by the location and by the nature of the inflammation. CD displays a transmural discontinuous inflammation, often with granulomas, in any part of the digestive system (most often ileum and/or colon). UC is almost exclusively restricted to the colon with a continuous superficial mucosal and submucosal inflammation. Both CD and UC can be further subphenotyped, suggesting that there is heterogeneity within each disorder. Despite many clinical and pathological features that distinguish CD and UC, the collective term inflammatory bowel disease (IBD) is often used for the two diseases. Clustering of IBD in families without specificity for a given form of IBD supports the notion of common genetic factors in the etiologies of the two conditions. In addition, higher concordance rates in monozygotic twins than dizygotic twins, particularly in CD, points to the importance of genes [1]. Recent advances in genetics have proven that both CD and UC are truly polygenic, but there are also strong environmental influences on IBD. This notion is first and foremost supported by the rapid increase in incidence of IBD during the past 50 years. Understanding the complex interplay between genetic and environmental factors that lead to IBD is a formidable challenge. Animal models have been very helpful in this respect, providing fundamental insight into the importance of immunologic dysregulation and intestinal microbiota [2,3]. Animal models are continuing to give new insights into the pathogenesis of IBD, as shown by two recent papers in PLoS Medicine [4,5]. Simultaneously, there have been remarkable advances in the understanding of the genetics of human IBD, and the mapping of IBD genes is continuously progressing [6–8]. The new genetic findings bear promise for new and better therapies. This translation of basic science into the clinic will be much facilitated by relevant and good animal models. We can thus expect that the new genetic findings will set the stage for future development of animal models in IBD.