MRL狼疮小鼠中DNA甲基化水平的改变。
Alteration of DNA methylation levels in MRL lupus mice.
作者信息
Mizugaki M, Yamaguchi T, Ishiwata S, Shindo H, Hishinuma T, Nozaki S, Nose M
机构信息
Department of Pharmaceutical Sciences, Tohoku University Hospital, Miyagi, Japan.
出版信息
Clin Exp Immunol. 1997 Nov;110(2):265-9. doi: 10.1111/j.1365-2249.1997.tb08326.x.
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.
最近的报告表明，DNA甲基化与自身免疫性疾病的病因有关。我们以MRL/lpr小鼠品系作为模型，研究了狼疮小鼠品系中DNA甲基化水平的变化，该品系会出现年龄依赖性淋巴结病和自身免疫性疾病。处于自身免疫性疾病状态的20周龄MRL/lpr小鼠胸腺和腋窝淋巴结的DNA甲基化水平低于尚无症状的4周龄MRL/lpr小鼠。在至少20周内看起来正常的MRL/+品系小鼠中未观察到显著变化，而两个品系小鼠脾脏中的DNA甲基化水平从4周龄到20周龄均显著增加。然而，在MRL品系中，随着年龄增长外周血中的DNA甲基化水平未观察到显著变化。此外，我们阐明，给予5-氮杂胞苷对MRL/lpr小鼠的长期存活有显著影响，并降低了腋窝淋巴结和脾脏中的DNA甲基化水平。本文讨论了DNA甲基化水平与自身免疫性疾病进展可能的相关性。
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