MRL mice produce anti-Su autoantibody, a specificity associated with systemic lupus erythematosus

Certain autoimmune mouse strains exhibit features similar to human SLE. To discover genetic and immunologic events governing expression of a new SLE-associated antibody, the presence of anti-Su and its relationship to other SLE-related antibodies (anti-Sm, -ribonucleoprotein, -Ro (SS-A), -La (SS-B)) were determined in MRL and other autoimmune and nonautoimmune mice. By double immunodiffusion, sera from 34/183 (19%) 4- to 10-mo-old MRL/Mp-lpr/lpr (MRL/lpr) and 28/108 (26%) 8- to 20-mo-old MRL/Mp(-)+/+ (MRL/+) mice were positive for anti-Su antibodies. Anti-Sm antibodies were found in 60/183 (33%) and 39/108 (36%) of these animals, respectively. The two specificities were found together in individual mice more frequently than would be predicted by chance. In contrast, C57BL/6-lpr/lpr (B6/lpr) mice rarely showed either specificity. Analysis of F1 hybrids between B6/lpr and MRL/lpr and of F1 x MRL/lpr backcross mice suggested that a small number of autosomal recessive genes controlled the anti-Su and anti-Sm responses. With the exception of a single NZB serum sample, NZB, BXSB, and nonautoimmune mice were negative for all antibodies tested, and no mice were positive for anti-RNP, anti-Ro, or anti-La. MRL/lpr and MRL/+ autoimmune mice thus provide unique models for human SLE, because they express several of the SLE-specific marker autoantibodies. These models should be useful in disclosing molecular and immunologic events governing autoantibody expression in this condition.