MRL mice, an inbred strain derived from several other strains, develop ANAs and late onset glomerulonephritis reminiscent of SLE. A spontaneously occuring mutation led to impressive lymphoproliferation (lpr mutation), severe, early onset nephritis closely resembling proliferative lupus nephritis, the development of erosive arthritis (more characteristic of RA than SLE), salivary gland inflammation (reminiscent of Sjogren’s syndrome), vasculitis, and skin disease resembling cutaneous lupus. Both MRL and MRL lpr/lpr mice develop a host of autoantibodies characteristic of SLE, including anti-Sm and anti-dsDNA as well as severe hyper gammaglobulinemia. These autoantibodies develop earlier in the presence of the lpr mutation, which generally accelerates the onset of lupus-like disease in this strain. The abnormalities caused by the lpr mutation are due to an ETn retrotransposon insertion into the Fas gene, which encodes an important protein mediator of apoptosis. Defective apoptois of lymphocytes leads to the accumulation of CD3CD4CD8 (“double negative”) T cells, accounting for the massive lymphoproliferation seen in MRL lpr/lpr mice.