A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis
Article first published online: 1 AUG 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 8, pages 2332–2342, August 2003
How to Cite
Olofsson, P., Lu, S., Holmberg, J., Song, T., Wernhoff, P., Pettersson, U. and Holmdahl, R. (2003), A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis. Arthritis & Rheumatism, 48: 2332–2342. doi: 10.1002/art.11100
- Issue published online: 1 AUG 2003
- Article first published online: 1 AUG 2003
- Manuscript Accepted: 14 APR 2003
- Manuscript Received: 7 FEB 2003
- Anna Greta Crafoord Foundation for Rheumatological Research
- King Gustaf V's 80-Year Foundation
- Kock and Österlund Foundations
- Swedish Association Against Rheumatism
- Swedish Medical Research Council
- European Union project. Grant Number: QLG1-CT2001-01407
- Swedish Foundation for Strategic Research
- Beijer Foundation
- Nilsson-Ehle Foundation
- Swedish Society for Medical Research
To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristane-induced arthritis (PIA) in rats.
A genome-wide linkage analysis of an (E3 × DA)DA backcross of rats with CIA (n = 364 male rats; the same strain combinations as previously used to determine the genetic control of PIA) was performed. The strongest loci in both CIA and PIA (i.e., Cia12/Pia4 and Cia13/Pia7) were isolated in congenic strains. Susceptibility in both congenic strains was tested in rats with CIA and in rats with PIA.
We found a striking, although not complete, similarity of the arthritis-controlling loci in CIA and in PIA, as well as the previously defined loci associated with cartilage destruction, antibody production, and the acute-phase response. All major PIA quantitative trait loci (QTLs) identified in early severe arthritis were also strong regulators of CIA. The 2 strongest QTLs, Cia12/Pia4 on chromosome 12 and Cia13/Pia7 on chromosome 4, were also analyzed in congenic strains with DA or E3 as the background genome. Consistent with the results of linkage analysis, the congenic strain experiments showed that the chromosome 4 locus was more penetrant in CIA than in PIA, while the chromosome 12 locus almost completely dominated the control of PIA severity.
The underlying genetic control of CIA was found to have many, but not all, pathogenic mechanisms in common with PIA, despite the use of a cartilage-specific antigen (type II collagen) to induce CIA but not PIA.