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

Author

Listed:
  • Riham Smoom

    (The Hebrew University of Jerusalem)

  • Catherine Lee May

    (University of Pennsylvania)

  • Vivian Ortiz

    (University of Pennsylvania
    Hospital of the University of Pennsylvania)

  • Mark Tigue

    (University of Pennsylvania)

  • Hannah M. Kolev

    (University of Pennsylvania)

  • Melissa Rowe

    (University of Pennsylvania)

  • Yitzhak Reizel

    (University of Pennsylvania
    Faculty of Biotechnology and Food Engineering)

  • 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)

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.

Suggested Citation

  • 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. Kaes, 2023. "Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42534-6
    DOI: 10.1038/s41467-023-42534-6
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    References listed on IDEAS

    as
    1. Tsung-Po Lai & Ning Zhang & Jungsik Noh & Ilgen Mender & Enzo Tedone & Ejun Huang & Woodring E. Wright & Gaudenz Danuser & Jerry W. Shay, 2017. "A method for measuring the distribution of the shortest telomeres in cells and tissues," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    2. Han-Woong Lee & Maria A. Blasco & Geoffrey J. Gottlieb & James W. Horner & Carol W. Greider & Ronald A. DePinho, 1998. "Essential role of mouse telomerase in highly proliferative organs," Nature, Nature, vol. 392(6676), pages 569-574, April.
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    Cited by:

    1. Tobias T. Schmidt & Carly Tyer & Preeyesh Rughani & Candy Haggblom & Jeffrey R. Jones & Xiaoguang Dai & Kelly A. Frazer & Fred H. Gage & Sissel Juul & Scott Hickey & Jan Karlseder, 2024. "High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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