Here, we have utilized mouse models bearing these lupus susceptibility loci to investigate the therapeutic potential of Btk in a spontaneous murine model of lupus nephritis by treating the mice with a small molecule Btk-inhibitor, PCI-32765; this is an irreversible inhibitor that binds covalently to Cys-481 of Btk with an IC50 of about 0.5 nM in biochemical assays. This evidence concerns the gene BTK and systemic lupus erythematosus.