Svenson John L, EuDaly Jackie, Ruiz Phil, Korach Kenneth S, Gilkeson Gary S
Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, PO Box 250637, Charleston, SC 29425, USA.
Clin Immunol. 2008 Aug;128(2):259-68. doi: 10.1016/j.clim.2008.03.508. Epub 2008 May 29.
Systemic lupus erythematosus (SLE) occurs nine times more often in females than males. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ER alpha deficient NZM females, but not males, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ER alpha deficient MRL/lpr female, but not male, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ER beta had no effect on disease in either strain or sex. Taken together, these data demonstrate a key role for ER alpha, but not ER beta, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice.
系统性红斑狼疮（SLE）在女性中的发病率是男性的九倍。本研究的目的是确定雌激素受体（ER）无效基因型对易患狼疮的新西兰黑鼠2410（NZM）和MRL/lpr小鼠疾病的影响，以此作为界定雌激素受体信号在狼疮中作用的一种方法。与野生型小鼠相比，ERα缺陷的NZM雌性小鼠（而非雄性小鼠）生存期显著延长，蛋白尿、肾脏病理评分和血清尿素氮水平降低，尽管血清抗双链DNA水平较高。ERα缺陷的MRL/lpr雌性小鼠（而非雄性小鼠）蛋白尿和肾脏病理评分也显著降低，对自身抗体水平无影响。ERβ缺陷对两种品系和两种性别的疾病均无影响。综上所述，这些数据表明，在雌性NZM和MRL/lpr小鼠中，ERα而非ERβ在狼疮样疾病而非自身免疫的发生发展中起关键作用。
