Alteration of DNA methylation levels in MRL lupus mice |
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| Authors: | M MIZUGAKI T YAMAGUCHI S ISHIWATA H SHINDO T HISHINUMA S NOZAKI M NOSE |
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| Affiliation: | Department of Pharmaceutical Sciences, Tohoku University Hospital, Miyagi, Japan;*Pharmacy Division, Ohta Nishinouchi Hospital, Fukushima, Japan;†Department of Pathology, Tohoku University School of Medicine, Miyagi, Japan |
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| 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. |
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| Keywords: | DNA methylation 5-methyldeoxycytidine 5-azacytidine MSUMp-lpr/lpr mice autoimmune disease |
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