Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83 Huddinge, Sweden.
Biochem Biophys Res Commun. 2012 Aug 10;424(4):710-6. doi: 10.1016/j.bbrc.2012.07.016. Epub 2012 Jul 16.
Estrogen receptor alpha (ERα) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ERα mouse line that can be used to knock out ERα in selected tissues by using the Cre/LoxP system. In this study, we established a new ERα knockout mouse line by crossing the floxed ERα mice with Cre deleter mice. Here we show that genetic disruption of the ERα gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ERα is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.
雌激素受体 alpha（ERα）是一种核受体，可响应雌激素调节多种生理过程。为了研究其生物学作用，我们构建了一种 floxed ERα 小鼠品系，可通过 Cre/LoxP 系统在特定组织中敲除 ERα。在这项研究中，我们通过将 floxed ERα 小鼠与 Cre 缺失小鼠杂交，建立了一种新的 ERα 敲除小鼠品系。结果显示，所有组织中 ERα 基因的遗传缺失导致雌雄小鼠均不育。子宫和卵巢的组织学检查显示，子宫严重萎缩，卵巢出现出血性囊肿。这些结果表明，雌性小鼠的不育是由于生殖道功能缺陷所致。此外，雌性敲除小鼠表现为高血糖、肥胖，并且在 4 月龄时，与野生型同窝仔鼠相比，这些小鼠的体重增加了 20%以上，且这一差异随时间推移而增加。我们的研究结果表明，ERα 对于生殖道发育是必需的，并且作为女性代谢的调节剂具有重要功能。
