Complex genetic control in a rat model for rheumatoid arthritis

We have defined previously five quantitative trait loci controlling development of pristane-induced arthritis in a cross between E3 and DA rats. To define new loci controlling the disease we have mapped three recombinant inbred strains between DA and E3 and analysed an F2 cross between DA rats and one of these RI strains. Two novel loci affecting, disease severity are identified on chromosome 1 (Pia8) and chromosome 4 (Pia7) respectively. We could also reproduce the earlier identified Pia3 locus on chromosome 6 associated with arthritis onset. In the original E3 x DA F2 cross, neither of the loci Pia7, Pia8, or Pia1 showed any association with arthritis. To investigate the possibility of interacting loci preventing the phenotypic expression of other loci, the E3xDA F2 cross was re-analysed with a model for a two locus interaction, knowing the presence of these newly identified loci. We found suggestive evidence for an interaction where an effect of Pia7 and Pia1 on disease severity depends on DA homozygosity at specific loci, which themselves do not confer susceptibility. This shows that additional disease associated loci can be identified if other loci are neutralized. This will be of importance for understanding the complex genetics controlling rheumatoid arthritis. (C) 2000 Academic Press.