Identification of intervals on chromosomes 1, 3, and 13 linked to the development of lupus in BXSB mice

Objective. To identify intervals containing systemic lupus erythematosus (S LE) susceptibility alleles in the BXSB strain of mice. Methods, We analyzed 286 (B10 x [B10 x BXSB]F-1) backcross mice for a range of phenotypic traits associated with the development of SLE in BXSB mice. The mice were genotyped using 93 microsatellite markers, and the linkage of these markers to disease was studied by extreme-phenotype and quantitative trait locus analysis. Results. The disease phenotype in these backcross mice was less severe than that in BXSB mice. However, antinuclear antibody production was increased compared with the parental strain, We identified 4 areas of genetic linkage to disease on chromosome 1 (Bxs1-4), 1 on chromosome 3 (Bxs5), and another interval on chromosome 13 which were associated with various aspects of th e phenotype. Bxs4 and Bxs5 are located in regions not previously linked to disease in other models of SLE. Conclusion. SLE in the BXSB mouse model has a complex genetic basis and inv olves at least 5 distinct intervals located on chromosomes 1 and 3. There i s evidence that different intervals affect particular aspects of the SLE ph enotype.