Complex genetic control in a rat model for rheumatoid arthritis

We have defined previously five quantitative trait loci controlling develop ment of pristane-induced arthritis in a cross between E3 and DA rats. To de fine new loci controlling the disease we have mapped three recombinant inbr ed strains between DA and E3 and analysed an F2 cross between DA rats and o ne of these RI strains. Two novel loci affecting, disease severity are iden tified on chromosome 1 (Pia8) and chromosome 4 (Pia7) respectively. We coul d also reproduce the earlier identified Pia3 locus on chromosome 6 associat ed with arthritis onset. In the original E3 x DA F2 cross, neither of the l oci Pia7, Pia8, or Pia1 showed any association with arthritis. To investiga te 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 l ocus interaction, knowing the presence of these newly identified loci. We f ound suggestive evidence for an interaction where an effect of Pia7 and Pia 1 on disease severity depends on DA homozygosity at specific loci, which th emselves do not confer susceptibility. This shows that additional disease a ssociated loci can be identified if other loci are neutralized. This will b e of importance for understanding the complex genetics controlling rheumato id arthritis. (C) 2000 Academic Press.