Two Major Interacting Chromosome Loci Control Disease Susceptibility in Murine Model of Spondyloarthropathy

摘要: Autoimmune spondylitis was induced in BALB/c mice and their MHC-matched (BALB/c × DBA/2)F 1 F 2 hybrids by systemic immunization with cartilage/intervertebral disk proteoglycan (PG). As human ankylosing spondylitis, the MHC major permissive genetic locus murine PG-induced (PGIS). Two non-MHC chromosome loci highly significant linkage were found on chromosomes ( Pgis2 ) 18 Pgis1 accounting for 40% of entire trait variance. The dominant spondylitis-susceptibility allele is derived from strain, whereas recessive present disease-resistant DBA/2 strain. significantly affected disease-controlling locus, inducing as high incidence spondylitis-susceptible parent Additional suggestive mapped to 12, 15, 19. Severity positively correlated serum levels amyloid A, IL-6, Pg-specific Abs, showed negative correlation Ag-induced T cell proliferation, IFN-γ, IL-4, TNF-α production. A controlling IL-6 14 near osteoclast differentiation factor Tnfsf11 . Locus 11 Stat3 Stat5 genes controlled level Ig IgG2a isotype. two homologous regions genome, which control patients. Thus, this animal model experimentally might facilitate identification humans.