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Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1
Telomeres, the ends of eukaryotic chromosomes, protect genome integrity and enable cell proliferation. Maintaining optimal telomere length in the germline and throughout life limits the risk of cancer and enables healthy aging. Telomeres in the house mouse, Mus musculus, are about five times longer...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593777/ https://www.ncbi.nlm.nih.gov/pubmed/37872177 http://dx.doi.org/10.1038/s41467-023-42534-6 |
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author | Smoom, Riham May, Catherine Lee Ortiz, Vivian Tigue, Mark Kolev, Hannah M. Rowe, Melissa Reizel, Yitzhak Morgan, Ashleigh Egyes, Nachshon Lichtental, Dan Skordalakes, Emmanuel Kaestner, Klaus H. Tzfati, Yehuda |
author_facet | Smoom, Riham May, Catherine Lee Ortiz, Vivian Tigue, Mark Kolev, Hannah M. Rowe, Melissa Reizel, Yitzhak Morgan, Ashleigh Egyes, Nachshon Lichtental, Dan Skordalakes, Emmanuel Kaestner, Klaus H. Tzfati, Yehuda |
author_sort | Smoom, Riham |
collection | PubMed |
description | Telomeres, the ends of eukaryotic chromosomes, protect genome integrity and enable cell proliferation. Maintaining optimal telomere length in the germline and throughout life limits the risk of cancer and enables healthy aging. Telomeres in the house mouse, Mus musculus, are about five times longer than human telomeres, limiting the use of this common laboratory animal for studying the contribution of telomere biology to aging and cancer. We identified a key amino acid variation in the helicase RTEL1, naturally occurring in the short-telomere mouse species M. spretus. Introducing this variation into M. musculus is sufficient to reduce the telomere length set point in the germline and generate mice with human-length telomeres. While these mice are fertile and appear healthy, the regenerative capacity of their colonic epithelium is compromised. The engineered Telomouse reported here demonstrates a dominant role of RTEL1 in telomere length regulation and provides a unique model for aging and cancer. |
format | Online Article Text |
id | pubmed-10593777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105937772023-10-25 Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 Smoom, Riham May, Catherine Lee Ortiz, Vivian Tigue, Mark Kolev, Hannah M. Rowe, Melissa Reizel, Yitzhak Morgan, Ashleigh Egyes, Nachshon Lichtental, Dan Skordalakes, Emmanuel Kaestner, Klaus H. Tzfati, Yehuda Nat Commun Article Telomeres, the ends of eukaryotic chromosomes, protect genome integrity and enable cell proliferation. Maintaining optimal telomere length in the germline and throughout life limits the risk of cancer and enables healthy aging. Telomeres in the house mouse, Mus musculus, are about five times longer than human telomeres, limiting the use of this common laboratory animal for studying the contribution of telomere biology to aging and cancer. We identified a key amino acid variation in the helicase RTEL1, naturally occurring in the short-telomere mouse species M. spretus. Introducing this variation into M. musculus is sufficient to reduce the telomere length set point in the germline and generate mice with human-length telomeres. While these mice are fertile and appear healthy, the regenerative capacity of their colonic epithelium is compromised. The engineered Telomouse reported here demonstrates a dominant role of RTEL1 in telomere length regulation and provides a unique model for aging and cancer. Nature Publishing Group UK 2023-10-23 /pmc/articles/PMC10593777/ /pubmed/37872177 http://dx.doi.org/10.1038/s41467-023-42534-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Smoom, Riham May, Catherine Lee Ortiz, Vivian Tigue, Mark Kolev, Hannah M. Rowe, Melissa Reizel, Yitzhak Morgan, Ashleigh Egyes, Nachshon Lichtental, Dan Skordalakes, Emmanuel Kaestner, Klaus H. Tzfati, Yehuda Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title | Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title_full | Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title_fullStr | Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title_full_unstemmed | Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title_short | Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 |
title_sort | telomouse—a mouse model with human-length telomeres generated by a single amino acid change in rtel1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593777/ https://www.ncbi.nlm.nih.gov/pubmed/37872177 http://dx.doi.org/10.1038/s41467-023-42534-6 |
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