Mapping colitis susceptibility in mouse models: distal chromosome 3 contains major loci related to Cdcs1

Abstract

Inflammatory bowel disease (IBD) summarizes a group of chronic intestinal disorders with Crohn's disease and ulcerative colitis being most prominent. Though much effort is put into identification of causative factors, its etiology is still not understood. Risk factors for disease development include genetic predisposition and environmental triggers. Crucial for identification and analysis of relevant factors are mouse models. Experimental IBD in mice occurs spontaneously or is induced by chemicals, cell transfer, pathogens, or genetic mutation. These models were utilized for analyzing genetic contribution to disease and genotype-environmental interactions. In these studies, a variety of modifier loci were identified, thereby demonstrating the complexity of disease. A major contribution of distal chromosome 3 was independently replicated in several studies. The first colitogenic QTL in this region was detected using the IL-10-deficient mouse model and called cytokine deficiency-induced colitis susceptibility (Cdcs)1. This quantitative trait locus contains at least three subintervals with independent genetic factors. This locus or defined subintervals were replicated in at least seven studies, using models based on dysregulation of innate or adaptive immunity or pathogen control. In this review we illustrate the various models used for genetic mapping of susceptibility to experimental IBD and display Cdcs1-related loci as well as the mechanism of their contribution identified so far.