Mutations in the estrogen receptor α (ERα) occur in endocrine-resistant metastatic breast cancer. However, a major gap persists with the lack of genetically tractable immune competent mouse models to study disease. Hence, we developed a Cre-inducible murine model expressing a point-activated ESR1^Y541S (ESR1^Y537S in humans) driven by its endogenous promoter. Germline expression of mutant ESR1^Y541S reveals dramatic developmental defects in the reproductive organs, mammary glands, and bones of the mice. These observations provide critical insights into the tissue-specific roles of ERα during development and highlights the potential use of our model in further developmental and cancer studies.

中文翻译：

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点激活ESR1Y541S对性二态性器官的发育具有显著作用。

雌激素受体α（ERα）的突变发生在耐内分泌的转移性乳腺癌中。但是，由于缺乏研究疾病的具有遗传学上可操纵的免疫能力的小鼠模型，因此仍然存在重大差距。因此，我们开发了一种Cre可诱导的小鼠模型，该模型表达了由其内源启动子驱动的点激活ESR1 ^Y541S（^人中为ESR1 ^Y537S）。突变ESR1 ^Y541S的生殖细胞表达表明，小鼠生殖器官，乳腺和骨骼发育^异常。这些观察结果提供了对ERα在发育过程中组织特异性作用的重要见解，并突出了我们的模型在进一步的发育和癌症研究中的潜在用途。