Cartilage oligomeric matrix protein induction of chronic arthritis in mice.
(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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https://lup.lub.lu.se/record/1168431
- author
- Carlsén, Stefan LU ; Kutty Selva, Nandakumar LU ; Bäcklund, Johan LU ; Holmberg, Jens LU ; Hultqvist, Malin LU ; Vestberg, Mikael LU and Holmdahl, Rikard LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 58
- issue
- 7
- pages
- 2000 - 2011
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000257469800015
- pmid:18576344
- scopus:47249098355
- pmid:18576344
- ISSN
- 1529-0131
- DOI
- 10.1002/art.23554
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- 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
- 2016-04-01 11:32:59
- date last changed
- 2022-02-03 01:17:16
@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 Inc.}},
series = {{Arthritis and Rheumatism}},
title = {{Cartilage oligomeric matrix protein induction of chronic arthritis in mice.}},
url = {{http://dx.doi.org/10.1002/art.23554}},
doi = {{10.1002/art.23554}},
volume = {{58}},
year = {{2008}},
}