POLYGENIC CONTROL OF SUSCEPTIBILITY TO MURINE SYSTEMIC LUPUS-ERYTHEMATOSUS

Susceptibility to glomerulonephritis (GN) and anti-dsDNA autoantibody production was analyzed in crosses with a newly developed systemic lup us erythematosus-susceptible inbred strain, NZM/Aeg2410. The mode of i nheritance and the number and location of systemic lupus erythematosus -associated susceptibility loci were analyzed by interval mapping in a backcross with C57BL/6. Three chromosomal intervals containing strong recessive GN susceptibility alleles were identified on chromosomes 1, 4, and 7, each containing several potentially interesting candidate g enes. Heterozygosity at H-2 was also found to correlate strongly with GN susceptibility, consistent with previous findings in the NZB/NZW pa rental strain model. Logistic regression analysis indicated that each of these susceptibility alleles independently accounted for a componen t of GN susceptibility, and that susceptibility was inherited as a thr eshold genetic liability in this model system.