Ram Raj Singh, MD, University of California at Los Angeles

"Mechanisms of Organ Damage in Males with Lupus Nephritis"

2008 Novel Pilot Projects Program

Although systemic lupus erythematosus (SLE) affects women much more frequently than men, men with SLE experience more severe organ damage. The goal of the current proposal is to investigate the contribution of sex chromosomes in increased organ damage in males with SLE. Studies over the last 30 years have focused on the role of sex hormones in conferring gender differences in SLE. However, extensive studies suggest that sex hormonal effects do not fully account for the profound gender differences seen in SLE. This Project uses a unique model system that will allow investigators to understand the role of sex chromosomes in the absence of confounding effects of sex hormones. These unique strains have been created in a way that mice with both XX and XY sex chromosomes have ovaries. Analogously, strains have been created where mice with both XX and XY chromosomes have testes. The investigators will also evaluate the effect of a gene on X chromosome that might contribute to increased organ damage in males with SLE. The results of the proposed study will not only aid our understanding of lupus, but will also potentially lead to identification of newer targets of treatment.