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Updated: Jan 16, 2026
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
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Genetic Engineering of Humanized Telomere Mice.
Fan Zhang1, De Cheng1,2, Kenneth I Porter1
1Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
Bio-Protocol
|September 26, 2025
Summary
Researchers created humanized telomere mice (HuT mice) to better study human aging. These mice exhibit progressive telomere shortening, mimicking human telomere dynamics for aging and disease research.
Area of Science:
- Genetics
- Molecular Biology
- Aging Research
Background:
- Telomere shortening is a key indicator of human aging and limits cell proliferation (Hayflick limit).
- Mouse models have limitations for studying human telomere biology due to species-specific differences in telomere dynamics and telomerase regulation.
Purpose of the Study:
- To engineer a mouse model that accurately recapitulates human telomere length dynamics and telomerase regulation.
- To develop a robust platform for investigating human aging and related diseases.
Main Methods:
- Utilized CRISPR-Cas9 and homologous recombination to knock in large genomic fragments (~47 kb).
- Engineered a humanized telomerase gene (hmTert) by replacing mouse regulatory sequences with human ones in the mouse Tert locus.
- Developed successive generations of genetically modified mice (HuT mice).
Main Results:
- Achieved progressive telomere shortening across generations in HuT mice.
- Telomere lengths in HuT mice reached human-like lengths (below 10 kb).
- Successfully recapitulated human TERT regulation and telomere length dynamics in mice.
Conclusions:
- The developed HuT mouse model provides a valuable tool for studying human telomere biology.
- This model facilitates research into aging processes and age-related diseases with greater accuracy.
- The protocol enhances success rates for knocking in large genomic fragments using CRISPR-Cas9 and homologous recombination.
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