# A mouse model with humanized telomere homeostasis

> **NIH NIH R56** · WASHINGTON STATE UNIVERSITY · 2021 · $313,650

## 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.
Consequently, telomeres progressively shortened upon successive cell divisions and function
as an aging clock. Accordingly, telomere shortening is a critical factor of human aging and
telomerase activation is essential for the development of most human cancers. On the other
hand, some 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. Here, 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. In this application, we propose the following 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 telomere homeostasis.

## Key facts

- **NIH application ID:** 10490487
- **Project number:** 1R56AG073423-01
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** JIYUE ZHU
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,650
- **Award type:** 1
- **Project period:** 2021-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490487

## Citation

> US National Institutes of Health, RePORTER application 10490487, A mouse model with humanized telomere homeostasis (1R56AG073423-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10490487. Licensed CC0.

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