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

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(Y5...

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Detalles Bibliográficos
Autores principales: Simond, Alexandra M., Ling, Chen, Moore, Michaela J., Condotta, Stephanie A., Richer, Martin J., Muller, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528702/
https://www.ncbi.nlm.nih.gov/pubmed/32912899
http://dx.doi.org/10.1101/gad.339424.120
Descripción
Sumario: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.