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Updated: Jun 3, 2026
Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
Published on: November 3, 2013
Myogenin regulates denervation-dependent muscle atrophy in mouse soleus muscle
Peter C D Macpherson1, Xun Wang, Daniel Goldman
1Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Abstract:
Muscle inactivity due to injury or disease results in muscle atrophy. The molecular mechanisms contributing to muscle atrophy are poorly understood. However, it is clear that expression of atrophy-related genes, like Atrogin-1 and MuRF-1, are intimately tied to loss of muscle mass. When these atrophy-related genes are knocked out, inactive muscles retain mass. Muscle denervation stimulates muscle atrophy and Myogenin (Myog) is a muscle-specific transcription factor that is highly induced following muscle denervation. To investigate if Myog contributes to muscle atrophy, we have taken advantage of conditional Myog null mice. We show that in the denervated soleus muscle Myog expression contributes to reduced muscle force, mass, and cross-sectional area. We found that Myog mediates these effects, at least in part, by regulating expression of the Atrogin-1 and MuRF-1 genes. Indeed Myog over-expression in innervated muscle stimulates Atrogin-1 gene expression and Myog over-expression stimulates Atrogin-1 promoter activity. Thus, Myog and the signaling cascades regulating its induction following muscle denervation may represent novel targets for therapies aimed at reducing denervation-induced muscle atrophy.
Insights
Myogenin (Myog) drives muscle atrophy by increasing atrophy-related genes. Inhibiting Myog signaling may offer new therapies for muscle loss due to denervation.
Area of Science:
- Muscle physiology
- Molecular biology
- Biochemistry
Background:
- Muscle inactivity leads to atrophy, a poorly understood condition.
- Atrophy-related genes, such as Atrogin-1 and MuRF-1, are linked to muscle mass loss.
- Muscle denervation triggers atrophy, with Myogenin (Myog) being a key induced transcription factor.
Purpose of the Study:
- To investigate the role of Myogenin (Myog) in muscle atrophy following denervation.
- To explore the molecular mechanisms by which Myog influences muscle mass and function.
Main Methods:
- Utilized conditional Myog null mice to study denervation-induced muscle atrophy.
- Analyzed muscle force, mass, and cross-sectional area in denervated soleus muscles.
- Investigated the regulation of Atrogin-1 and MuRF-1 gene expression by Myog.
Main Results:
- Myog expression significantly contributed to reduced muscle force, mass, and cross-sectional area in denervated soleus muscles.
- Myog was found to mediate these effects, at least partly, by regulating Atrogin-1 and MuRF-1 gene expression.
- Overexpression of Myog in innervated muscle stimulated Atrogin-1 gene expression and promoter activity.
Conclusions:
- Myogenin plays a critical role in mediating denervation-induced muscle atrophy.
- Myog's regulation of Atrogin-1 and MuRF-1 highlights its importance in muscle mass maintenance.
- Myog and its upstream signaling pathways represent potential therapeutic targets for combating muscle atrophy.
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