MULTIPLE LUPUS SUSCEPTIBILITY LOCI MAP TO CHROMOSOME-1 IN BXSB MICE

BXSB mice spontaneously develop a lupus-like syndrome that is accelera ted by the Yaa gene CY-linked autoimmune accelerator). We studied the phenotype of disease in CB10 x BXSB)F-1 and (BXSB x CB10 x BXSB)F-1) b ackcross mice and genotyped 224 backcross animals to allow a microsate llite-based genome-wide linkage analysis to be conducted, In the backc ross population, three intervals on chromosome 1 showed significant li nkage to disease, suggesting that multiple loci contribute to the prod uction of autoimmune disease. D1Mit5 at 32.8 cM was linked to developm ent of nephritis (chi(2) = 15.68, p = 7.5 x 10(-5)), as was D1Mit12 at 63.1 cM (chi(2) = 20.17, p = 7.1 x 10(-6)). D1Mit403 at 100 cM was li nked to anti-dsDNA Ab production (chi(2) = 17.28, p = 3.2 x 10(-5)). S uggestive linkages to antinuclear Abs and nephritis were identified on chromosome 3, to splenomegaly on chromosome 4, and to anti-ssDNA Ab p roduction on chromosome 10, Chromosome 4 and the telomeric region of c hromosome 1 have previously been linked to disease in other mouse mode ls of systemic lupus erythematosus; however, the centromeric regions o f chromosome 1 and chromosomes 3 and 10 are unique to BXSB, This impli es that, though some loci may be common to a number of mouse models of lupus, different clusters of disease genes confer disease susceptibil ity in different strains of mice.