Sex-dependent systemic lupus erythematosus-like syndrome in (NZB X SJL)F1 mice.

(NZB X SJL)F1 (NS) mice were previously shown to develop sex-dependent thymic abnormalities in the course of aging. The possible occurrence in these mice of various autoimmune manifestations characteristic of a systemic lupus erythematosus (SLE)-like syndrome is investigated. Female NS mice died faster and exhibited antinuclear (AN), anti-ds-DNA antibodies and circulating immune complexes earlier in life and in greater amounts than male NS mice. At 12 months of age immunoglobulin deposits were detected in the renal glomeruli and at the dermo-epidermal junction of the skin. These deposits were more frequent and more intense in females than in males. In addition, proteinuria was found to rise with aging in females but not in males. These data demonstrate that NS mice suffer from SLE symptoms which, like the thymic abnormalities, are influenced by sex-related factors. The study of castrated males and females and of androgen-treated females suggests that androgens exert an inhibitory effect on these SLE symptoms. Preliminary genetic analysis further indicates a probable polygenic control of these SLE symptoms in NS females.