Generating Transgenic Mouse Models for Studying Celiac Disease

Abstract

This chapter provides a brief overview of current animal models for studying celiac disease, with a focus on generating HLA transgenic mouse models. Human Leukocyte Antigen class II molecules have been a particular target for transgenic mice due to their tight association with celiac disease, and a number of murine models have been developed which had the endogenous MHC class II genes replaced with insertions of disease susceptible HLA class II alleles DQ2 or DQ8. Additionally, transgenic mice that overexpress interleukin-15 (IL-15), a key player in the inflammatory cascade that leads to celiac disease, have also been generated to model a state of chronic inflammation. To explore the contribution of specific bacteria in gluten-sensitive enteropathy, the nude mouse and rat models have been studied in germ-free facilities. These reductionist mouse models allow us to address single factors thought to have crucial roles in celiac disease. No single model has incorporated all of the multiple factors that make up celiac disease. Rather, these mouse models can allow the functional interrogation of specific components of the many stages of, and contributions to, the pathogenic mechanisms that will lead to gluten-dependent enteropathy. Overall, the tools for animal studies in celiac disease are many and varied, and provide ample space for further creativity as well as to characterize the complete and complex pathogenesis of celiac disease.