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. 1997 Nov;110(2):265–269. doi: 10.1111/j.1365-2249.1997.tb08326.x

Alteration of DNA methylation levels in MRL lupus mice

M MIZUGAKI *, T YAMAGUCHI *, S ISHIWATA *, H SHINDO *, T HISHINUMA *, S NOZAKI *, M NOSE †
PMCID: PMC2265501  PMID: 9367411

Abstract

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/4- 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.

Keywords: DNA methylation, 5-methyldeoxycytidine, 5-azacytidine, MSUMp-lpr/lpr mice, autoimmune disease

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