Cartilage oligomeric matrix protein induction of chronic arthritis in mice.

Abstract

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 Ncf1 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)F1, (BALB/c x B10.Q)F1, Ncf1 mutated, H-2Aq, H-2Ap, 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-2q and H-2p MHC haplotypes allowed the initiation of COMPIA. Using H-2Aq-transgenic and H-2Ap-transgenic mice, we demonstrated a role of both the Aq and Ep class II molecules in this model. Interestingly, the introduction of a mutation in the Ncf1 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.

• Authors: Stefan Carlsen, Kutty Selva Nandakumar, Johan Bäcklund, Jens Holmberg, Malin Hultqvist, Mikael Vestberg, Rikard Holmdahl
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 58 Issue 7 Pg. 2000-11 (Jul 2008) ISSN: 0004-3591 [Print] United States
• PMID: 18576344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Cartilage Oligomeric Matrix Protein
• Extracellular Matrix Proteins
• Glycoproteins
• Matn1 protein, mouse
• Matrilin Proteins
• TSP5 protein, human
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Animals
• Antibodies (blood)
• Arthritis (blood, chemically induced, immunology)
• Cartilage Oligomeric Matrix Protein
• Disease Models, Animal
• Extracellular Matrix Proteins (adverse effects, blood, immunology)
• Female
• Glycoproteins (adverse effects, blood, immunology)
• Humans
• Major Histocompatibility Complex (genetics)
• Matrilin Proteins
• Mice
• NADPH Oxidases (metabolism)
• Rats