Jakacka Monika, Ito Masafumi, Martinson Fred, Ishikawa Toshio, Lee Eun Jig, Jameson J Larry
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Mol Endocrinol. 2002 Oct;16(10):2188-201. doi: 10.1210/me.2001-0174.
We created a nonclassical estrogen receptor (ER) knock-in mouse model by introducing a mutation that selectively eliminates classical ER signaling through estrogen response elements, while preserving the nonclassical ER pathway. Heterozygous nonclassical ER knock-in (NERKI) females are infertile. Their ovaries contain no corpora lutea, reflecting a defect in ovulation, and the stromal cells contain lipid droplets, suggesting altered steroidogenesis. The uteri are enlarged with evidence of cystic endometrial hyperplasia, and the mammary glands are hypoplastic. These phenotypic features indicate differential ER effects on growth and development in various estrogen-responsive tissues. These findings suggest that nonclassical ER signaling pathways play an important physiological role in the development and function of the reproductive system.
我们通过引入一种突变创建了一种非经典雌激素受体（ER）敲入小鼠模型，该突变可选择性消除通过雌激素反应元件的经典ER信号传导，同时保留非经典ER途径。杂合子非经典ER敲入（NERKI）雌性小鼠不育。它们的卵巢中没有黄体，这反映出排卵存在缺陷，并且基质细胞含有脂滴，表明类固醇生成发生了改变。子宫增大，有囊性子宫内膜增生的迹象，乳腺发育不全。这些表型特征表明ER对各种雌激素反应性组织的生长和发育有不同的影响。这些发现表明，非经典ER信号通路在生殖系统的发育和功能中发挥着重要的生理作用。
