Enhanced susceptibility to lupus contributed from the nonautoimmune C57BL/10, but not C57BL/6, genome

Genes from New Zealand Black and New Zealand White mice have been implicated in the development of a disease similar to human systemic lupus erythematosus. In an attempt to define the MBC class II genes involved in disease, we previously studied similarly designed backcrosses of New Zealand Black-mice with C57BL/6 (B6) mice transgenic for E-z genes or with C57BL/10 (B10) mice transgenic for A(z) genes. Although the transgenes showed no effect on the development of autoantibody production or lupus nephritis in either backcross, surprisingly, there,vas greatly increased expression of these disease traits in the backcrosses involving BIO compared with B6 mice. These studies therefore implicated genetic contributions in E10 vs B6 backgrounds, despite their 98% identity. A genome-wide linkage analysis uncovered a B10 locus on mid-chromosome 13, which enhanced nephritis and was strongly linked with the production of pathogenic retroviral gp70-anti-gp70 immune complexes when contributed by B10, but not B6, mice. The subsequent identification of a single marker polymorphic between B10 and B6, along,vith the extreme genetic similarity between the two strains in this region, is likely to permit expedited identification of the lupus-susceptibility gene from this nonautoimmune strain.