LOCALIZATION OF QUANTITATIVE TRAIT LOCI REGULATING ADJUVANT-INDUCED ARTHRITIS IN RATS - EVIDENCE FOR GENETIC-FACTORS COMMON TO MULTIPLE AUTOIMMUNE-DISEASES

Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune e xperimental model with many features similar to rheumatoid arthritis ( RA), To identify potential genetic regulatory mechanisms in IM, we con ducted genome-wide linkage analysis in F-2 progeny of arthritis-suscep tible Dark Agouti (DA) and relatively resistant Fischer 344 (F344) inb red rats. We compared the data with our previously reported investigat ion of collagen-induced arthritis (CIA), which was expanded in the fol low-up study reported in this work. We found two quantitative trait lo ci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the MHC, and Aia3/Cia3 on chromosome 4, We also identified a second un ique QTL in AIA, Aia2, on chromosome 4, Interestingly, the QTL region on chromosome 4 (Aia3/Cia3), like the MHC, appears to he involved in s everal other autoimmune diseases in rats, including insulin-dependent diabetes, thyroiditis, and experimental autoimmune uveitis, Moreover, an analysis of conserved synteny among rats, mice, and humans suggeste d that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain candidate genes for several autoimmune/inflammatory diseases in mice and humans, includin g diabetes, systemic lupus erythematosus, inflammatory bowel disease, asthma/atopy, multiple sclerosis, and RA, The rat models appear to pro vide a powerful complementary approach to identify and characterize ca ndidate genes that may contribute to autoimmune diseases in several sp ecies.