P099 Myd88 gene knockout inhibits the development of lupus-like disease in NZB/W F1 mice

Abstract

The New Zealand Black (NZB) × New Zealand White (NZW) F1 hybrid female mice (NZB/WF1) develop a disease closely resembling human systemic lupus erythematosus (SLE), characterized by the production of antinuclear antibodies, severe glomerulonephritis and early mortality. Recently, innate immune responses have been reported to play an important role in the development of autoimmune disease. In this study we investigated the role of Myd88 protein (an important regulator of innate immune signaling pathways) in the pathogenesis of lupus-like disease in Myd88 knockout NZB/W F1 mice. The Myd88-deficient mice were backcrossed separately in the NZB and NZW backgroud. Heterozygous NZB as well as NZW of F10 backcross generation were intercrossed to achieve Myd88 -/- NZB/W F1 mice (KO) and Myd88 +/+ NZB/W F1 mice (WT). WT and Myd88 KO mice were compared for serum concentrations of anti-dsDNAantibody, biochemical markers of active disease (BUN, Cr, Alb, TP, T-CHO, protein urea), histological analysis of kidney pathology and mortality. Compared with WT mice, Myd88 KO mice featured significantly reduced serum concentrations of anti-dsDNAantibody, reduced levels of biochemical markers of active disease, reduced kidney pathology and reduced mortality. Our result indicates that innate immunity participates in the pathogenesis of lupus prone mice and Myd88 is its important regulator.