A non-major histocompatibility locus determines tissue specificity in the pathogenic process underlying synovial proliferation in a mouse arthropathy model

Background: The incidence and characteristics of spontaneous ankylosis in the ankle of specific F₁ mice descended from two Fas-deficient strains were reported. Here the coincidence of synovial proliferation and ankylosis in the descendent F₂ mice is reported. Aim: To clarify whether the two distinct manifestations are genetically different. Methods: An arthropathic group of mice (MCF₂) were bred by intercrossing MRL/Mp.Fas^lpr-sap^-/sap^- and C3H/He.Fas ^lpr mice. All mice were killed by bleeding under anaesthesia when they were 6 months old. Pathological grades for synovial proliferation were determined by microscopical examination. To obtain a linkage locus, the whole genome of male MCF₂ mice was scanned by using 73 microsatellite markers. Results: Synovial proliferation was equally observed in male and female MCF₂ mice. No correlation was observed between the grades of synovial proliferation and the ankylosis occurring in the MCF₂ mice. A suggestive susceptibility locus was shown in the middle of chromosome 11. This locus was an MRL allele with a recessive inheritance mode. Conclusion: The pathogenic mechanisms of synovial proliferation and ankylosis are genetically different. The present locus is overlapped with some loci associated with rheumatoid arthritis and with others associated with experimental arthritides.