Immunogenetics of Experimentally Induced Arthritis

Astounding advances in biotechnology and swift accumulation of detailed information about genome sequences of different species, human and mouse in particular, lead us to believe that the time when we will know all genes controlling complex autoimmune diseases is very close. Indeed, our understanding of molecular mechanisms involved in immune regulation and immunogenetics has greatly improved during the last few years. However, the most recent progress rather underlines the distance between our skills showing the relevance of known or artificial alteration in a single gene for the formation of morbid phenotype, and our abilities to find out how natural variations in the genome might affect disease development. Thus, finding cryptic disease-susceptibility genes controlling complex autoimmune diseases, such as rheumatoid arthritis, is still an extremely challenging mission. Multiple-gene effects, phenocopies, heterogeneity of the human population, and the influence of poorly understood environmental factors make this task even more difficult. Experimentally induced autoimmune arthritis in murine strains, basically mimicking human disease, is based on a clean genetic background and a fully controllable environmental milieu. Through the dissection of the genetic background of the murine proteoglycan-induced arthritis we can bridge a gap to the understanding of human disease.