PATHOGENESIS OF MURINE SYSTEMIC LUPUS ERYTHEMATOSUS

Scripps Research Institute, La Jolla CA

Investigators

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Abstract

DESCRIPTION: (Adapted from the Investigator's abstract): Genetic susceptibility is the major predisposing factor thus far identified for spontaneous systemic lupus erythematosus (SLE) in both humans and animal models of the disease. Previously, the investigator identified in an (NZB x NZW)F2 intercross 8 loci designated Lbw1-Lbw8 on chromosomes 17, 4, 5, 6, 7, 18, 1, and 11, respectively, that exhibited evidence of linkage to one or more of four major SLE disease traits. Five of these loci have been confirmed in other crosses. The investigator has generated congenic lines for Lbw2, a locus on chromosomes 4 required for hemolytic anemia, and Lbw5, a locus on chromosome 7. Lbw5 is an autoimmune accelerator that increases the production of IgG autoantibodies and promotes hemolytic anemia, glomerulonephritis and early mortality in NZB mice. In this application the investigator proposes to: 1) define the genetics of immunoglobulin and autoantibody responses and the relationship of autoantibody specificity to other traits. This will be done by linkage analysis using an expanded set of BWF2 mice; 2) generate congenic lines for Lbw1, 2, 4, 5 and 7 to examine the effects of susceptibility and resistance alleles at these loci on clinical and immunologic manifestations; and 3) undertake positional cloning of Lbw2 and Lbw5.