Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene-induced arthritis

Several quantitative trait loci (QTLs) regulating the risk of experimental arthritis have been identified by genome-wide linkage analyses, but only th e MHC has thus far been reported to transfer arthritis susceptibility in co ngenic animals, We have produced a congenic strain for Oia3, a genetic fact or originally identified as an oil-induced arthritis (OIA) QTL in arthritis -prone DA rats, A 46 cM telomeric region of chromosome in encompassing Oia3 was transferred from DA rats to MHC-identical but minutely arthritis-susce ptible LEW.1AV1 rats by selective breeding. Arthritis development was provo ked in Oia3-congenic rats by intradermal injection of different adjuvant oi ls, One successful arthritis trigger was squalene, which is approved for va ccinations in humans and has been implicated in Gulf War syndrome. The endo genous cholesterol precursor squalene induced T cell infiltration into join ts and macroscopic arthritis in Oia3congenic rats and DA rats, whereas LEW. 1AV1 rats were almost resistant. Arthritis onset, similar to 14 days postin jection, coincided with arrested body-weight gain and increased plasma leve ls of the inflammation markers fibrinogen and al-acid glycoprotein, Congeni c rats displayed intermediate phenotypes compared with the two parental str ains, and similar to rheumatoid arthritis in humans, female preponderance w as observed in Oia3congenic rats. Finally, recombinant rat strains were con structed and were used to map a susceptibility gene(s) in females to a telo meric 4-19 cM Oia3 subregion, The experimental system described allows tran sformation of multifactorial arthritis susceptibility into dichotomous phen otypes.