Aged B6.SB-Yaa/J Mice develop an SLE-like Disease (130.11)

Abstract

Abstract Mouse models of SLE are considered pivotal in understanding the genetics of SLE along with identifying targets for therapy. Male mice of the BXSB/MpJ recombinant inbred strain, first described by Murphy and Roths in 1978, develop a spontaneous and severe SLE-like syndrome resulting in death averaging ~6 months of age, while females show only a very chronic syndrome. A mutant locus found on the Y chromosome is, therefore, appropriately named the Y-linked autoimmune accelerator (Yaa). Previous analysis have suggested that Yaa fails to induce an SLE-like disease in B6 mice, the caveat to this being that the SLE criteria analyzed were limited to serological analysis, histopathology, and mortality on mice up to 8–12 months of age. We report here that when mice of a significantly older age, 15–24 months, are compared to age-matched B6 controls, the B6.SB-Yaa/J mice clearly developed an SLE-like disease. This is characterized by significant splenomegaly, monocytosis, immune cells with an activation phenotype, the presence of homogeneous anti-nuclear antibody staining, glomerulonephritis, decreased weight and survival as well as a gene expression signature similar to BXSB/MpJ mice. These results suggest that Yaa alone is sufficient to induce an SLE-like syndrome in aged B6 mice. Funded by NIH R21DK074463 and DK56597 to DCR, Arthritis Foundation to JAB.