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Cartilage oligomeric matrix protein induction of chronic arthritis in mice

Carlsén, Stefan (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
Nandakumar, Kutty Selva, 1965- (author)
Karolinska Institutet,Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
Bäcklund, Johan (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
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Holmberg, Jens (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
Hultqvist, Malin (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
Vestberg, Mikael (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
Holmdahl, Rikard (author)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund; Karolinska Institutet, Stockholm, Sweden
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 (creator_code:org_t)
Wiley, 2008
2008
English.
In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:7, s. 2000-2011
  • Journal article (peer-reviewed)
Abstract Subject headings
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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 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)
art (subject category)

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