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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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:
Research Communication
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
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author Simond, Alexandra M.
Ling, Chen
Moore, Michaela J.
Condotta, Stephanie A.
Richer, Martin J.
Muller, William J.
author_facet Simond, Alexandra M.
Ling, Chen
Moore, Michaela J.
Condotta, Stephanie A.
Richer, Martin J.
Muller, William J.
author_sort Simond, Alexandra M.
collection PubMed
description 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.
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spelling pubmed-75287022021-04-01 Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs Simond, Alexandra M. Ling, Chen Moore, Michaela J. Condotta, Stephanie A. Richer, Martin J. Muller, William J. Genes Dev Research Communication 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. Cold Spring Harbor Laboratory Press 2020-10-01 /pmc/articles/PMC7528702/ /pubmed/32912899 http://dx.doi.org/10.1101/gad.339424.120 Text en © 2020 Simond et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Simond, Alexandra M.
Ling, Chen
Moore, Michaela J.
Condotta, Stephanie A.
Richer, Martin J.
Muller, William J.
Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title_full Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title_fullStr Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title_full_unstemmed Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title_short Point-activated ESR1(Y541S) has a dramatic effect on the development of sexually dimorphic organs
title_sort point-activated esr1(y541s) has a dramatic effect on the development of sexually dimorphic organs
topic Research Communication
url 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
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