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ARTHRITIS AND RHEUMATISM
卷 58, 期 7, 页码 2000-2011出版社
WILEY-BLACKWELL
DOI: 10.1002/art.23554
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Objective. To develop a new mouse model for arthritis using cartilage oligomeric matrix protein (COMP) and to study the role of major histocompatibility complex (MHC) and Ncfl genes in COMP-induced arthritis (COMPIA). Methods. Native (pentameric) and denatured (monomeric) COMP purified from a rat chondrosarcoma was injected into mice with Freund's adjuvant to induce arthritis. C3H.NB, C3H.Q, B10.P, B10.Q, (B10.Q x DBA/1)F(1), (BALB/c x B10.Q)F(1), Ncfl mutated, H-2A(q) H-2A(p), and human DR4+-transgenic mice were used. Anti-COMP antibodies and COMP levels in the immune sera were analyzed, and passive transfer of arthritis with purified immune sera was tested. Results. Immunization with rat COMP induced a severe, chronic, relapsing arthritis, with a female preponderance, in the mice. The disease developed in C3H.NB mice, but not in B10.P mice, although they share the same MHC haplotype. Both H-2(q) and H-2(p) MHC haplotypes allowed the initiation of COMPIA. Using H-2A(q)-transgenic and H-2A(p)-transgenic mice, we demonstrated a role of both the A(q) and E(p) class II molecules in this model. Interestingly, the introduction of a mutation in the Ncfl gene, which is responsible for the reduced oxidative burst phenotype, into the COMPIA-resistant B10.Q mouse strain rendered them highly susceptible to arthritis. In addition, the transfer of anti-COMP serum was found to induce arthritis in naive mice. Mice transgenic for the rheumatoid arthritis (RA)-associated DR4 molecule were found to be highly susceptible to COMPIA. Conclusion. Using rat COMP, we have developed a new and unique mouse model of chronic arthritis that resembles RA. This model will be useful as an appropriate and alternative model for studying the pathogenesis of RA.
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