Scientia Agricultura Sinica ›› 2014, Vol. 47 ›› Issue (8): 1577-1587.doi: 10.3864/j.issn.0578-1752.2014.08.014

• ANIMAL SCIENCE·VETERINARY SCIENCERE·SOURCE INSECT • Previous Articles     Next Articles

Myostatin and Its Double-Muscling Phenotype in Animals

 WANG  Jian-Qi, CAO  Wen-Guang   

  1. Institute of Animal Sciences and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing 100193
  • Received:2013-08-27 Online:2014-04-15 Published:2014-01-03

Abstract: Myostatin (MSTN), also known as growth differentiation factor 8(GDF-8), is a member of the transforming growth factor β(TGF-β) superfamily, which was first obtained from screening a murine skeletal muscle complementary DNA library in 1997. The gene of MSTN consists of three exons and two introns, the gene is very conservative as only three or fewer differences exist among the amino acid sequences of mature peptide in all studied species. High levels of expression of MSTN has been found mainly in skeletal muscle although it is expressed in multiple tissues, including the cardia, adipose, placenta, mammary gland, uterus, olfactory neuron, liver, spleen, lung, and kidney, etc. The mature MSTN is liberated as a homogeneous dimer from prepromyostatin through proteolytic processing of signal peptidase, furin and BMP-1/tolloid family. MSTN acts as a strong autocrine/paracrine negative regulator of muscle growth. It inhibits the proliferation and differentiation of myoblast cells through activating TGF-β, p38 MAPK, ERK1/2 and JNK signal pathway, and inhibiting IGF-AKT and Wnt signal pathway. MSTN also regulates glucose uptake and metabolism in the muscle cell. Myostatin-null animals showed significant increased muscle mass, that is double-muscling phenotype, improved muscle healing through enhancing regeneration and reducing fibrosis, etc; reduced adipogenesis and consequently decreased leptin secretion, and enhanced thermogenesis through driving browning of white adipose tissue; increased bone density and bone mineral content, and increased fracture callus size and strength for fracture healing. Naturally occurred loss-of-function mutations in the MSTN gene have also been shown to underlie the double-muscling phenotype in mammals. Such known mutations are found in several species including p.D273RfsX13(nt821(del11)), p.C313Y, p.F140X(nt419(del7–ins10)), p.Q204X, p.E226X and p.E291X in cattle, c.960delG(p.K320NfsX39) and c.120insA(p.N40MfsX9)in sheep, c.939-940delTG in dogs and c.373+5G>A in human. In targeting the MSTN gene in sheep, a gain-of-function miRNA mutation, c.2360G>A(g.6223G>A), can also show double-muscling phenotype. Double-muscled animals not only have more muscle, but also have less bone, less fat. Therefore, it has been a hot topic to optimize the functions of MSTN and reduce the side effects of double-muscling phenotype with genetic engineering techniques to breed preeminent table-purpose livestock. For example, a conservative missense mutation p.F94L exists in cattle, which does not alter the function of MSTN and has no side effects of double-muscling phenotype, but showed increased muscle mass and decreased fat depth and intramuscular fat content, and had no significant effect in birth and growth traits. In brief, investigation into MSTN will not only give a chance to further elucidate the mechanism involved in muscle growth, but may also help to breed animals. This review summaries the structure, signal pathway, phenotype, mutants, and the mechanism of the MSTN in mammals and their implications in livestock.

Key words: myostatin/GDF-8 , double-muscling phenotype , mammalian , loss-of-function mutations

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