Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length

Fan Zhang, Cheng De, Kenneth I. Porter, Emily A. Heck, Shuwen Wang, Hui Zhang, Christopher J. Davis, Gavin P. Robertson and Jiyue Zhu ()
Additional contact information
Fan Zhang: Washington State University
Cheng De: Washington State University
Kenneth I. Porter: Washington State University
Emily A. Heck: Washington State University
Shuwen Wang: Washington State University
Hui Zhang: Washington State University
Christopher J. Davis: Washington State University
Gavin P. Robertson: Pennsylvania State University College of Medicine
Jiyue Zhu: Washington State University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Telomeres shorten with each cell division, serving as biomarkers of aging, with human tissues exhibiting short telomeres and restricted telomerase expression. In contrast, mice have longer telomeres and widespread telomerase activity, limiting their relevance as models for human telomere biology. To address this, we engineer a mouse strain with a humanized mTert gene (hmTert), replacing specific non-coding sequences with human counterparts. The hmTert gene, which is repressed in adult tissues except the gonads and thymus, closely mimics human TERT regulation. This modification rescues telomere dysfunction in mTert-knockout mice. Successive intercrosses of Terth/- mice stabilized telomere length below 10 kb, while Terth/h mice achieve a human-like average length of 10–12 kb, compared to 50 kb in wildtype mice. Despite shortened telomeres, Terth/h mice maintain normal body weight and cell homeostasis. These mice, with humanized telomere regulation, represent a valuable model to study human aging and cancer.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56559-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56559-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56559-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().