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

• Published in: The American journal of the medical sciences 2004-04, Vol.327 (4), p.188-195
• Main Authors: Adarichev, V.A., Nesterovitch, A.B., Jacobs, J.J., Glant, T.T., Szanto, S., Firneisz, G., Zhang, J., Mikecz, K., Finnegan, A., Oswald, J.P.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Antibodies - metabolism; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Collagen-induced arthritis; Cytokines - immunology; Cytokines - metabolism; Disease Susceptibility; Diseases of the osteoarticular system; General aspects; Genetic Linkage; Genome screen; Humans; Inflammatory joint diseases; Major Histocompatibility Complex; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Proteoglycan-induced arthritis; Proteoglycans - immunology; Proteoglycans - toxicity; Quantitative Trait Loci; Rheumatoid arthritis; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/00000441-200404000-00004

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-2d) BALB/c × DBA/2 and MHC-unmatched (H-2d/H-2q) 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 × 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.