Differential effect of the autoimmune yaa and ipr genes on the acceleration of lupus‐like syndrome in mrl/mpj mice

The Yaa gene (Y chromosome‐linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive Ipr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus‐like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and Ipr genes in the development of the autoimmune syndrome, the Ychromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus‐like nephritis in MRL mice was investigated in comparison with those bearing the Ipr mutation. The Yaa gene as well as the Ipr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus‐like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the Ipr gene (50% mortality rate: 7 months). This may be related to the finding that the Ipr gene enhanced the production of a large spectrum of autoantibodies, including anti‐DNA, rheumatoid factors and anti‐gp70, and of cryoglobulins, whereas only anti‐gp70 production among the autoantibodies studied was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW x MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the Ipr gene, exhibits selective autoimmune accelerating activity, but as as result of increased formation of certain nephritogenic autoantibodies such as anti‐gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus‐like nephritis in lupus‐prone mice.