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Point-activated ESR1^Y541S has a dramatic effect on the development of sexually dimorphic organs.

ABSTRACT: 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.

SUBMITTER: Simond AM

PROVIDER: S-EPMC7528702 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Point-activated ESR1Y541S has a dramatic effect on the development of sexually dimorphic organs.

Simond Alexandra M AM Ling Chen C Moore Michaela J MJ Condotta Stephanie A SA Richer Martin J MJ Muller William J WJ

Genes & development 20200910 19-20

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 ESR1Y541S (ESR1Y537S in humans) driven by its endogenous promoter. Germline expression of mutant ESR1Y541S reveals dramatic developmental defects in the reproductive organs, ...[more]

PMID: 32912899

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