# A mouse model with humanized telomere homeostasis

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2022 · $461,767

## Abstract

Abstract
 The goal of this project is to develop a mouse model that acquires human-like telomere
homeostasis for the study of human aging, cancer, and other age-related diseases. In humans,
most somatic cells lack telomerase expression and cannot replenish their telomeres. Telomeres
progressively shorten upon successive cell divisions, functioning as an aging clock.
Consequently, telomere attrition is a critical factor of human aging and telomere stabilization,
predominantly via telomerase activation, is an essential event in the development of most
human cancers. On the other hand, many other organisms, including laboratory mice, do not
exhibit telomere-mediated replicative aging. Mice possess long telomeres and ubiquitous
telomerase activity in adult tissues. This interspecies difference has become a bottleneck for
addressing many fundamental questions in human aging and cancer biology using mouse
models. To tackle this challenge, we have started to create a mouse strain with humanized
telomere homeostasis. We have engineered a humanized mouse Tert allele (hmTert) by using
regulatory sequences from the human TERT gene (hTERT) to replace their mouse
counterparts. We found that the hmTert gene regulation recapitulated that of the hTERT gene
during mouse development and in mouse adult tissues. Remarkably, the hmTert allele imposed
a much shorter telomere length setpoint than the wildtype mTert gene in mice. In this application,
we propose three specific aims: 1) Create a mouse strain with hmTert alleles and human-like
short telomeres; 2) Study replicative aging in mice with humanized telomere homeostasis; and 3)
Determine lifespan and health-span of mice with humanized telomeres.

## Key facts

- **NIH application ID:** 10446393
- **Project number:** 1R01AG073423-01A1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** JIYUE ZHU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $461,767
- **Award type:** 1
- **Project period:** 2022-09-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446393

## Citation

> US National Institutes of Health, RePORTER application 10446393, A mouse model with humanized telomere homeostasis (1R01AG073423-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10446393. Licensed CC0.

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