SLE is a multi-organ autoimmune disease characterised by the presence of circulating autoantibodies to both naked DNA and nucleosomes. The pathogenesis is primarily related to the deposition of such immune complexes in tissues, with subsequent inflammation and organ damage. A breakdown in the physiological mechanisms by which nuclear antigens (eg naked DNA and nuclear DNA-protein complexes) are removed during cell death may allow the development of an inappropriate immune response against such intracellular components. The removal of DNA from nuclear antigens released during cell death is thought to be mediated predominantly by Dnase1, the major nuclease present in the serum and urine of both humans and mice. The development of Dnase1-deficient mice would therefore provide an ideal in vivo model to investigate these hypotheses further. To develop Dnase1-deficient mice by targeted gene deletion and to characterize the spontaneous phenotype.