Mouse models for genetic dissection of polygenic gastrointestinal diseases

Many diseases with a major public health impact are the result of complex interactions between environmental factors and multiple genes. In the past decade, methods for genome analysis, in particular quantitative trait locus (QTL) analysis in animal models, were developed to identify and localize the genes responsible for multifactorial (polygenic) diseases; QTL analysis is based on experimental crosses between inbred strains with high and low genetic susceptibility. Recently the genes underlying several QTLs could be cloned successfully. Here we describe the impact of these genomic approaches in mice on our understanding of the multifactorial genetics of three gastrointestinal diseases related to metabolism (cholesterol cholelithiasis), development (gastroschisis), and colorectal cancer. The examples demonstrate how mouse models continue to be an invaluable tool in unravelling complex pathomechanisms and unlocking our understanding of human diseases.