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Updated: Oct 4, 2026
Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies
Published on: January 31, 2013
Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old
G S Lynch1, R T Hinkle, J S Chamberlain
1Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109-2007, USA.
Abstract:
1. Differences in the effect of age on structure-function relationships of limb muscles of mdx (dystrophin null) and control mice have not been resolved. We tested the hypotheses that, compared with limb muscles from age-matched control mice, limb muscles of 6- to 17-month-old mdx mice are larger but weaker, with lower normalised force and power, whereas those from 24- to 28-month-old mdx mice are smaller and weaker. 2. The maximum isometric tetanic force (P(o)) and power output of limb muscles from 6-, 17-, 24- and 28-month-old mdx and control mice were measured in vitro at 25 degrees C and normalised with respect to cross-sectional area and muscle mass, respectively. 3. Body mass at 6 and 28 months was not significantly different in mdx and control mice, but that of control mice increased 16 % by 17 months and then declined 32 % by 28 months. The body masses of mdx mice declined linearly with age with a decrease of 25 % by 28 months. From 6 to 28 months of age, the range in the decline in the masses of EDL and soleus muscles of mdx and control mice was from 16 to 28 %. The muscle masses of mdx mice ranged from 9 % to 42 % greater than those of control mice at each of the four ages and, even at 28 months, the masses of EDL and soleus muscles of mdx mice were 17 % and 22 % greater than control values. 4. For mdx mice of all ages, muscle hypertrophy was highly effective in the maintenance of control values for absolute force for both EDL and soleus muscles and for absolute power of soleus muscles. Throughout their lifespan, muscles of mdx mice displayed significant weakness with values for specific P(o) and normalised power approximately 20 % lower than values for control mice at each age. For muscles of both strains, normalised force and power decreased approximately 28 % with age, and consequently weakness was more severe in muscles of old mdx than in those of old control mice.
Insights
Age impacts muscle function differently in mdx mice compared to controls. Despite larger muscles, mdx mice show consistent weakness, with age exacerbating this effect, leading to more severe decline in older mdx mice.
Area of Science:
- Muscle physiology
- Animal models of disease
- Age-related changes
Background:
- Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration.
- The mdx mouse is a common animal model for DMD, but age-related structure-function relationships in its limb muscles are not fully understood.
- Understanding these changes is crucial for developing effective therapies.
Purpose of the Study:
- To investigate age-dependent changes in limb muscle structure and function in mdx mice compared to age-matched controls.
- To test the hypothesis that younger mdx mice have larger but weaker muscles, while older mdx mice have smaller and weaker muscles.
- To determine how age affects normalized force and power in mdx mouse limb muscles.
Main Methods:
- In vitro measurement of maximum isometric tetanic force (Po) and power output in limb muscles (EDL and soleus) of mdx and control mice at 6, 17, 24, and 28 months of age.
- Normalization of force and power with respect to muscle cross-sectional area and mass, respectively.
- Comparison of body and muscle masses between mdx and control groups across different ages.
Main Results:
- Mdx mice exhibited larger muscle masses (9-42% greater) than controls across all ages, with EDL and soleus muscles being 17-22% larger even at 28 months.
- Despite muscle hypertrophy, mdx mice consistently showed ~20% lower specific force (normalized Po) and normalized power compared to controls.
- Normalized force and power decreased by ~28% with age in both mdx and control mice, with weakness being more pronounced in older mdx mice.
Conclusions:
- Muscle hypertrophy in mdx mice effectively maintains absolute force and soleus power but does not overcome inherent muscle weakness.
- Age-related decline in muscle function is present in both mdx and control mice, but it is more severe in older mdx mice.
- The study clarifies age-related structure-function dynamics in the mdx mouse model, highlighting persistent weakness and exacerbated age-related decline in dystrophin deficiency.
