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Cartilage oligomeric matrix protein induction of chronic arthritis in mice.

Carlsén, Stefan LU ; Kutty Selva, Nandakumar LU ; Bäcklund, Johan LU ; Holmberg, Jens LU ; Hultqvist, Malin LU ; Vestberg, Mikael LU and Holmdahl, Rikard LU (2008) In Arthritis and Rheumatism 58(7). p.2000-2011
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)F(1), (BALB/c x B10.Q)F(1), Ncf1 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... (More)
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)F(1), (BALB/c x B10.Q)F(1), Ncf1 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 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
58
issue
7
pages
2000 - 2011
publisher
John Wiley & Sons
external identifiers
  • wos:000257469800015
  • pmid:18576344
  • scopus:47249098355
ISSN
1529-0131
DOI
10.1002/art.23554
language
English
LU publication?
yes
id
ebca0c34-fad3-481a-b6f6-b5a4c99ee178 (old id 1168431)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18576344?dopt=Abstract
date added to LUP
2008-07-01 15:40:08
date last changed
2017-01-01 04:19:39
@article{ebca0c34-fad3-481a-b6f6-b5a4c99ee178,
  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)F(1), (BALB/c x B10.Q)F(1), Ncf1 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 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.},
  author       = {Carlsén, Stefan and Kutty Selva, Nandakumar and Bäcklund, Johan and Holmberg, Jens and Hultqvist, Malin and Vestberg, Mikael and Holmdahl, Rikard},
  issn         = {1529-0131},
  language     = {eng},
  number       = {7},
  pages        = {2000--2011},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Cartilage oligomeric matrix protein induction of chronic arthritis in mice.},
  url          = {http://dx.doi.org/10.1002/art.23554},
  volume       = {58},
  year         = {2008},
}