INTRODUCTION

The ultimate objective of biomedical research is to gain new understanding of the mechanisms of disease such that advances in treatment, and ultimately prevention and cure, are applied to that disease. However, progress is complicated by the inherent heterogeneity of human populations, even among those diagnosed with a particular disease. Even when appropriate study populations can be defined, access to the most relevant tissues and respect for patient privacy and autonomy present challenges to unfettered human-subject research. Although recent large-scale genomewide association studies in patients with systemic autoimmune diseases have identified candidate disease susceptibility genes, in vitro systems and experimental models are required to characterize the immunopathogenic significance of those genes and their products. Once targets for potential new therapies are identified, initial testing for toxicities of those therapeutics in humans is rarely appropriate. These limitations are among those that have led investigators to identify and to develop useful animal models that closely mimic human disease. Such models have been a particular focus of research relevant to the autoimmune rheumatic diseases. Although the use of animal models will always be limited by the likelihood of genetic and molecular distinctions between humans and lower mammals, current data from the analysis of the genomes of mice and man, including study of disease susceptibility loci, indicate that important hints regarding disease mechanisms can be gleaned from study of animal models. This chapter will review the major animal models investigators are using to explore the mechanisms of autoimmune rheumatic diseases, emphasizing the degree of fidelity of those models to the relevant human disease.