Disease-Associated Qualitative and Quantitative Trait Loci in Proteoglycan-Induced Arthritis and Collagen-Induced Arthritis

Two autoimmune murine models-proteoglycan (aggrecan)-induced arthritis (PGIA) and collagen-induced arthritis (CIA)-were developed in parent strains, F1 and F2 hybrids of major histocompatibility complex (MHC)-matched (H-2 ^d) BALB/c × DBA/2 and MHC-unmatched (H-2^d/H-2 ^q) BALB/c × DBA/1 intercrosses. The major goal of this comparative study was to identify disease (model)-specific (PGIA or CIA) and shared clinical and immunologic loci in 2 types of genetic intercrosses. Qualitative (binary/susceptibility) and quantitative (severity and onset) clinical trait loci were separated and analyzed independently or together with various pathophysiologic/immunologic traits, such as antigen-specific T- and B-cell responses and cytokine production. The major quantitative trait locus (QTL) was the MHC on chromosome 17, which was especially dominant in CIA. In addition, chromosomes 3, 5, 10, and X contained shared clinical loci in both models, and a total of 8 QTLs (clinical traits together with immunologic traits) were colocalized in PGIA and CIA.