title: Alteration of DNA methylation levels in MRL lupus mice.
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/+ 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.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, Miyagi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizugaki
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Ishiwata
authors.forename: H
authors.initials: H
authors.lastname: Shindo
authors.forename: T
authors.initials: T
authors.lastname: Hishinuma
authors.forename: S
authors.initials: S
authors.lastname: Nozaki
authors.forename: M
authors.initials: M
authors.lastname: Nose
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001835:Body Weight; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009929:Organ Size
chemical_list: D004247:DNA; D001374:Azacitidine