A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis.
OBJECTIVE
To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristane-induced arthritis (PIA) in rats.


METHODS
A genome-wide linkage analysis of an (E3 x 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.


RESULTS
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.


CONCLUSIONS
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.
Olofsson
Peter
P
Section for Medical Inflammation Research, Sölvegatan 19, I11 BMC, Lund University, S-22184 Lund, Sweden.
Lu
Shemin
S
Holmberg
Jens
J
Song
Tusheng
T
Wernhoff
Patrik
P
Pettersson
Ulf
U
Holmdahl
Rikard
R
D000818:Animals; D020296:Animals, Congenic; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000235:genetics*; D002813:Chondrosarcoma; D033481:Chromosomes, Mammalian / Q000235:genetics; D024043:Collagen Type II; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D007166:Immunosuppressive Agents; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes; D014407:Tumor Cells, Cultured
D024043:Collagen Type II; D007166:Immunosuppressive Agents; D013729:Terpenes; C009042:pristane