Alteration of DNA methylation levels in MRL lupus mice

Recent reports suggest that DNA methylation is involved in the cause of autoimmune disease. We investigated the alteration of DNA methylation levels in lupus strains of mice, MRL/lpr as a model, which develop an age-dependent lymphadenopathy and autoimmune disease. DNA methylation levels of thymus and axillary lymph nodes in 20-week-old MRL/lpr mice, which are in an autoimmune disease state, were lower than those of 4-week-old MRL/lpr mice with no symptoms as yet. No significant changes were observed in MRL/+ strain mice, which seemed normal at least 20 weeks, while DNA methylation levels in the spleen of both strains of mice increased significantly from the age of 4 to 20 weeks. However, no significant changes of DNA methylation levels in peripheral blood were observed with ageing in MRL strains. Moreover, we clarified that administration of 5-azacytidine had a strong effect on longer survival of MRL/lpr mice and reduced DNA methylation levels in the axillary lymph nodes and spleen. The possible relevance of DNA methylation levels to the progression of autoimmune disease is discussed.