Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1
Abstract 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 time...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42534-6 |
| _version_ | 1797558704247144448 |
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| author | Riham Smoom Catherine Lee May Vivian Ortiz Mark Tigue Hannah M. Kolev Melissa Rowe Yitzhak Reizel Ashleigh Morgan Nachshon Egyes Dan Lichtental Emmanuel Skordalakes Klaus H. Kaestner Yehuda Tzfati |
| author_facet | Riham Smoom Catherine Lee May Vivian Ortiz Mark Tigue Hannah M. Kolev Melissa Rowe Yitzhak Reizel Ashleigh Morgan Nachshon Egyes Dan Lichtental Emmanuel Skordalakes Klaus H. Kaestner Yehuda Tzfati |
| author_sort | Riham Smoom |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:34:48Z |
| format | Article |
| id | doaj.art-1ec8f8f1cc1c4bba80901ee1adb464df |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:34:48Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1ec8f8f1cc1c4bba80901ee1adb464df2023-11-20T09:53:36ZengNature PortfolioNature Communications2041-17232023-10-0114111810.1038/s41467-023-42534-6Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1Riham Smoom0Catherine Lee May1Vivian Ortiz2Mark Tigue3Hannah M. Kolev4Melissa Rowe5Yitzhak Reizel6Ashleigh Morgan7Nachshon Egyes8Dan Lichtental9Emmanuel Skordalakes10Klaus H. Kaestner11Yehuda Tzfati12Department of Genetics, The Silberman Institute of Life Sciences, Safra Campus, The Hebrew University of JerusalemDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics, The Silberman Institute of Life Sciences, Safra Campus, The Hebrew University of JerusalemDepartment of Genetics, The Silberman Institute of Life Sciences, Safra Campus, The Hebrew University of JerusalemDepartment of Pharmacology and Toxicology, Massey Cancer Center, Virginia Commonwealth UniversityDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of PennsylvaniaDepartment of Genetics, The Silberman Institute of Life Sciences, Safra Campus, The Hebrew University of JerusalemAbstract 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.https://doi.org/10.1038/s41467-023-42534-6 |
| spellingShingle | Riham Smoom Catherine Lee May Vivian Ortiz Mark Tigue Hannah M. Kolev Melissa Rowe Yitzhak Reizel Ashleigh Morgan Nachshon Egyes Dan Lichtental Emmanuel Skordalakes Klaus H. Kaestner Yehuda Tzfati Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1 Nature Communications |
| 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 |
| url | https://doi.org/10.1038/s41467-023-42534-6 |
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