Genetic control of arthritis in rats

This study was specifically designed to analyse the genetic control of the chronic disease course for the development of arthritis. Arthritis models w ith a chronic erosive arthritis are collagen induced arthritis induced with homologous collagen in oil but also arthritis induced with certain non-imm unogenic adjuvants such as pristane and avridine. In the presently describe d experiment we have used pristane induced arthritis. A single injection of 150 mu l pristane induces severe chronic arthritis in DA rats. The disease mimics rheumatoid arthritis in many aspects such as the chronic disease co urse, an erosive inflammation of peripheral joints, symmetric involvement o f the joints and the development of rheumatoid factors. To determine the ge netic contribution we have used a number of inbred, recombinant inbred and congenic strains as well as specifically designed segregating crosses. An i nfluence by the MHC region (designated Pia1 locus) on the chronic disease c ourse was determined through the uses of MHC congenic LEW strains in which the RT1-f haplotype conferred highest susceptibility. To map genes outside of MHC we used an F2 cross between the highly susceptible DA and the resist ant E3 strains; Loci exclusively associated with different phenotypes of th e disease could be identified: Arthritis onset (Pia2 and Pia3). Severity and joint erosions (Pia4). Chronicity (Pia5 and Pia6) and Pial (determined from MHC congenic strains) These findings demonstrates that a chronic self-perpetuative disease, mimic king rheumatoid arthritis, is controlled by different set of genes exclusiv ely linked to different phases of the disease course such as arthritis onse t, joint erosions, severity and chronicity.