GENETIC-LINKAGE OF IGG AUTOANTIBODY PRODUCTION IN RELATION TO LUPUS NEPHRITIS IN NEW-ZEALAND HYBRID MICE

F-1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mic e are a model of human systemic lupus erythematosus. These mice develo p a severe immune complex-mediated nephritis, in which antinuclear aut oantibodies are believed to play the major role. We used a genetic ana lysis of(NZB x NZW)F-1 x NZW backcross mice to provide insight into wh ether different autoantibodies are subject to separate genetic influen ces and to determine which autoantibodies are most important in the de velopment of lupus-like nephritis. The results showed one set of loci that coordinately regulated serum levels of IgG antibodies to double-s tranded DNA, single-stranded DNA, total histones, and chromatin, which overlapped with loci that were linked to the production of autoantibo dies to the viral glycoprotein, gp70. Loci linked with anti-gp70 compa red with antinuclear antibodies demonstrated the strongest linkage wit h renal disease, suggesting that autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contribute s to renal disease at a checkpoint distal to autoantibody production.