Myostatin’s Role in Genetic Control of Muscle Size and Strength

Authored by: Dustin S. Hittel

Routledge Handbook of Sport and Exercise Systems Genetics

Print publication date:  April  2019
Online publication date:  March  2019

Print ISBN: 9781138504851
eBook ISBN: 9781315146287
Adobe ISBN:


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Previous chapters have described the genetic, molecular, and neuroendocrine underpinnings of skeletal muscle size and strength and their response to exercise training. In this chapter, we discuss the specific role of myostatin, a protein that encompasses these three levels of control over muscle morphology and yet underscores the challenges and opportunities facing the nascent field of sport and exercise systems genetics. The transforming growth factor-beta (TGF-β) superfamily includes a diverse group of growth and differentiation factors that regulate embryonic development and subsequently, tissue homeostasis in adult animals (59). In 1997, Alexandra McPherron and Se-Jin Lee identified growth/differentiation factor-8 (GDF-8), a novel muscle-specific TGF-β family member that is expressed during embryogenesis and continues to be expressed by cells fated to the muscle lineage throughout development and into adulthood (13, 33). McPherron and Lee went on to characterize the developmental role of GDF-8 by disrupting the gene in mice, using targeted inactivation resulting in extremely hypermuscular animals with very low body fat. These findings determined that prenatal loss of GDF-8 liberates skeletal muscle growth through a combination of hypertrophy (an increase in the diameter of individual skeletal muscle fibers) and hyperplasia (an increase in the number of skeletal muscle fibers) (4, 6, 19, 32, 33, 37). Anecdotally, this gene was renamed myostatin (MSTN) in homage to a drug first appearing in “The Incredible Hulk” television series, but most likely owes this shared etymology with the Greek description of its role in skeletal muscle homeostasis (myo- (of muscle) stasis- (inactivity/inhibition)).

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