Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1

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 () and Yehuda Tzfati ()
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Riham Smoom: The Hebrew University of Jerusalem
Catherine Lee May: University of Pennsylvania
Vivian Ortiz: University of Pennsylvania
Mark Tigue: University of Pennsylvania
Hannah M. Kolev: University of Pennsylvania
Melissa Rowe: University of Pennsylvania
Yitzhak Reizel: University of Pennsylvania
Ashleigh Morgan: University of Pennsylvania
Nachshon Egyes: The Hebrew University of Jerusalem
Dan Lichtental: The Hebrew University of Jerusalem
Emmanuel Skordalakes: Virginia Commonwealth University
Klaus H. Kaestner: University of Pennsylvania
Yehuda Tzfati: The Hebrew University of Jerusalem

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42534-6

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