Our laboratory seeks to define the etiopathogenesis of systemic lupus erythematosus (SLE) and to identify potential therapeutic targets using lupus susceptible mice strains as model systems. Areas of interest related to lupus include systemic autoimmunity, tolerance, normal immune function, and genetics. A major focus is the identification of susceptibility genes in spontaneous lupus-prone mouse strains and in an induced model. Defining the genetic basis for lupus is critical for understanding lupus pathogenesis, as genetic susceptibility appears to be a prerequisite for disease development. Classical genetics approaches are being used to identify loci, narrow intervals with congenic mice, and identify genes. A second area of research seeks to identify the essential effector genes in SLE using both forward and reverse genetics approaches. These, in contrast to susceptibility genes, are typically normal genes that have non-redundant functions in disease pathogenesis. As such, their identification should yield important insights into disease processes and is also likely to have therapeutic implications. A third general area of interest is the study of specific pathways in lupus pathogenesis. Recent studies have investigated interferons, nucleic acid-recognizing toll-like receptors, actin cytoskeleton regulation, and mechanisms of B cell tolerance as they relate to systemic autoimmunity.