The McArdle’s Mouse Model: Providing Important Insight into Skeletal Muscle Regulation : Medicine & Science in Sports & Exercise

Journal Logo

BASIC SCIENCES: Commentary

The McArdle’s Mouse Model

Providing Important Insight into Skeletal Muscle Regulation

Lightfoot, J. Timothy Associate Editor

Author Information
Medicine & Science in Sports & Exercise: August 2016 - Volume 48 - Issue 8 - p 1447
doi: 10.1249/MSS.0000000000000960
  • Free

Most exercise physiologists’ exposure to patients with McArdle’s syndrome was through the groundbreaking work of Hagberg et al. (2) in 1982. Patients with McArdle’s disease experience a lack of myophosphorylase that in effect prevents the use of glycogen in the metabolic pathways and subsequently results in extreme exercise intolerance. Although these patients are fairly rare in the clinical world—the largest dataset published to date was in Medicine & Science in Sports & Exercise last year and only includes 81 patients (3)—patients with McArdle’s disease represent a fascinating model that can be used to investigate various physiological outcomes related to skeletal muscle metabolism dysfunction.

However, given the muscle metabolism limitations and general exercise intolerance (V˙O2max = 17.1 ± 5.3 mL·kg−1·min−1 [3]) of patients with McArdle’s disease, exercising these patients for research purposes is difficult, with the real possibility of exercise-induced conditions such as rhabdomyolysis to occur. These issues make patients with McArdle’s disease a vulnerable population and can put them under even stricter human subject compliance oversight and restrictions. Thus, the availability of a new McArdle’s mouse model that exhibits the same physiological pathology of human McArdle’s disease (4) enables the investigation of a wide variety of physiological mechanisms related to the role of glycogen in exercise metabolism and skeletal muscle functioning. An article in the current issue by the same group that developed the mouse model (1) provides a close look at many of the glycolysis regulatory mechanisms present in the skeletal muscle of patients with McArdle’s disease. For example, this article provides initial suggestions regarding whether the skeletal muscles of patients with McArdle’s disease can adapt to aerobic exercise or resistance training and the potential for a treatment that may improve the quality of life for patients with McArdle’s disease. Furthermore, given the more recent interest in muscle TORC and RAPTOR pathways in regulating muscle anabolism/catabolism, the authors’ results provide insight into how this loss-of-function mutation in glycogen usage affects these pathways.

Exercise physiology has many fascinating questions, many of which are unanswerable in a human model because of a variety of ethical and control reasons. However, the current article by Fiuza-Luces et al. (1) is a good example of how a loss-of-function animal model can provide important insight, research direction, and even treatment suggestions for human diseases and conditions. These types of models provide the critical translational research models that are so important in ultimately understanding human physiology.

REFERENCES

1. Fiuza-Luces C, Nogales-Gadea G, García-Consuegra I, Pareja-Galeano H, Pareja-Galeano H, Rufián-Vázquez L, et al. Muscle signaling in exercise intolerance: insights from the McArdle mouse model. Med Sci Sports Exerc. 2016;48(8):1448–58.
2. Hagberg JM, Coyle EF, Carroll JE. Exercise hyperventilation in patients with McArdle’s disease. J Appl Physiol Respir Environ Exerc Physiol. 1982;52:991–4.
3. Munguía-Izquierdo D, Santalla A, Lucia A. Cardiorespiratory fitness, physical activity, and quality of life in patients with McArdle disease. Med Sci Sports Exerc. 2015;47(4):799–808.
4. Nogales-Gadea G, Pinós T, Lucia A, et al. Knock-in mice for the R50X mutation in the PYGM gene present with McArdle disease. Brain. 2012;135:2048–57.
© 2016 American College of Sports Medicine