# TRANSGENIC MOUSE MODELS OF LONGEVITY

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1993 · $252,007

## Abstract

The process of aging is accompanied by a gradual decline in the
performance of most organ systems. The decreased mass and functional
capability of skeletal muscles contribute largely to the impairment of
locomotive performance that accompanies aging in both animals and humans.
Although age-related degeneration in muscle functions has been amply
documented, the molecular mechanisms underlying; selective muscle fiber
atrophy in aging mammals are currently unknown, and therefore therapeutic
courses aimed at maintaining functional and regenerative capacities in
aging muscles have been difficult to design.  The present study will
directly address the molecular basis of age-related atrophy in mammalian
skeletal muscle by investigating the function of a novel gene, c-ski, in
the selective maintenance of muscle fiber size, composition, and
regenerative capacity. Transgenic mice carrying extra copies of the c-ski
gene display cell hypertrophy of precisely those muscle fibers which are
most dramatically affected during the aging process.  Our recent
identification of a fiber-specific gene (myosin light chain) as the first
known genetic target for ski action in skeletal muscle cells has prompted
the experimental course outlined in this application. The first part of
the project will draw upon our extensive knowledge of myosin light chain
gene regulation, as well as the characterization of mouse lines both
carrying ski and myosin light chain transgenes, to build a molecular model
for the hypertrophic effects of ski gene expression, both in muscle cell
culture and in the aging animal. This model will provide the basic
information for our long-term research goal, to design a gene therapeutic
approach aimed at maintaining the integrity of the skeletal muscle system
in old age. The second part of the project exploits our experience with
analysis of gene expression and transgenic mouse technology, in
collaborative efforts with several laboratories.  Together we will assess
the potential effects of candidate longevity assurance genes on the
development and aging of transgenic animals, focussing our own analysis on
the skeletal musculature. Specifically, we will generate transgenic mice
carrying the mammalian homolog of LAG1, the first cloned longevity
assurance gene in yeast, and putative mammalian homologs to Drosophila
LAGs as they are identified. Characterization of these mice will provide
insights into the function of LAGs during development and in different
tissues, and will potentially comprise a valuable model for further study
of genetic parameters of longevity in mammals.

## Key facts

- **NIH application ID:** 3123950
- **Project number:** 1R01AG012316-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** Nadia A Rosenthal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $252,007
- **Award type:** 1
- **Project period:** 1993-09-30 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123950

## Citation

> US National Institutes of Health, RePORTER application 3123950, TRANSGENIC MOUSE MODELS OF LONGEVITY (1R01AG012316-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123950. Licensed CC0.

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