IDENTIFICATION OF FOUR NEW QUANTITATIVE TRAIT LOCI REGULATING ARTHRITIS SEVERITY AND ONE NEW QUANTITATIVE TRAIT LOCUS REGULATING AUTOANTIBODY PRODUCTION IN RATS WITH COLLAGEN-INDUCED ARTHRITIS

摘要: Objective Collagen-induced arthritis (CIA) is a polygenic model of experimentally induced autoimmunity and chronic joint inflammation. This study maps genetic loci that regulate CIA susceptibility in DA/Bkl (DA) BN/SsNHsd (BN) rats. Methods Genome scans covering chromosomes 1–20 interval mapping techniques using 159 simple sequence-length polymorphism markers were used to identify quantitative trait (QTLs) (DA × BN)F2 hybrids. Serum antibody titers type II collagen determined by enzyme-linked immunosorbent assay. Results DA rats high responders porcine (PII) developed severe (100%). BN low PII resistant (0%). genes strongly repressed PII-induced CIA. Only 12% BN)F1 (7 60) 31% (307 1,004) Three new QTLs (Cia11, Cia12, Cia13) with significant logarithm odds (LOD) scores 5.6, 4.6, 4.5, respectively, plus suggestive QTL (Cia14*, LOD 3.0) regulating severity identified on 3, 12, 4, 19. A QTL, Ciaa3, associating anticollagen titer (antibody 6.5; rat 5.2) mapped chromosome 9. Of 10 previously F344) ACI) rats, only Cia1 the major histocompatibility complex region coincident Cia5 (LOD >8.0) influenced rats. Conclusion Since exhibits many pathologic features rheumatoid arthritis, data indicate variety elements human autoimmune rheumatic diseases may be much larger more varied than originally envisioned.