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Updated: Jun 21, 2026
Isolation and Differentiation of Primary Myoblasts from Mouse Skeletal Muscle Explants
Published on: October 15, 2019
Relation between extent of myostatin depletion and muscle growth in mature mice
Stephen Welle1, Kerri Burgess, Charles A Thornton
1Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. stephen_welle@urmc.rochester.edu
Abstract:
Myostatin is a negative regulator of muscle growth and fiber size. Changes in myostatin expression might contribute to changes in muscle mass associated with various conditions, and reducing the amount of active myostatin is a potential strategy for preventing or reversing muscle atrophy. The present study was done to determine the extent to which myostatin levels must decline to induce growth of mature muscles. Myostatin expression was reduced by activating Cre recombinase in adult mice with floxed myostatin genes. The duration of Cre activation varied from 1 to 6 wk, and the residual myostatin mRNA expression after Cre activation varied from 3 to 63% of the normal level. Promyostatin levels declined in parallel with myostatin mRNA. There was no increase in muscle mass over the 3 mo following Cre activation if residual myostatin expression was >or=40% of normal. In mice with <40% of normal myostatin expression, muscle mass increased in proportion to the extent of myostatin depletion. In mice with
Insights
Significant reduction in myostatin levels is crucial for muscle growth. Depleting over 60% of myostatin in adult mice induced substantial muscle mass increase, highlighting its role in preventing muscle atrophy.
Area of Science:
- Muscle physiology
- Molecular biology
- Genetics
Background:
- Myostatin acts as a negative regulator of skeletal muscle growth.
- Reducing myostatin activity is a potential therapeutic strategy for muscle wasting conditions.
- Understanding the threshold of myostatin reduction needed for muscle growth is critical.
Purpose of the Study:
- To determine the minimum reduction in myostatin levels required to stimulate muscle growth in mature mice.
- To investigate the relationship between the extent of myostatin depletion and the resulting increase in muscle mass.
- To explore the molecular mechanisms underlying myostatin-induced muscle hypertrophy.
Main Methods:
- Adult mice with floxed myostatin genes had myostatin expression reduced via Cre recombinase activation.
- The duration of Cre activation was varied (1-6 weeks) to achieve different levels of residual myostatin mRNA (3-63%).
- Muscle mass, myonuclear domain volume, and RNA to myonuclei ratio were assessed over 3 months.
Main Results:
- No muscle mass increase was observed if residual myostatin expression remained above 40% of normal.
- Muscle mass increased proportionally to myostatin depletion when levels fell below 40%.
- Complete myostatin depletion (≤10% residual) resulted in approximately 25% muscle mass increase, enhanced transcription, and maintained Akt/mTOR and p38 MAPK pathways.
Conclusions:
- Substantial reduction (over 60%) of active myostatin is necessary to induce significant muscle growth in mature animals.
- Anabolic therapies targeting myostatin require significant myostatin removal or inactivation for efficacy.
- Myostatin depletion promotes muscle hypertrophy primarily by enhancing DNA transcription.
