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Gene Review

Mstn  -  myostatin

Mus musculus

Synonyms: Cmpt, GDF-8, Gdf8, Growth/differentiation factor 8, Myostatin
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Disease relevance of Gdf8


High impact information on Gdf8

  • This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep [6].
  • We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene [6].
  • The functional improvement of dystrophic muscle by myostatin blockade provides a novel, pharmacological strategy for treatment of diseases associated with muscle wasting such as DMD, and circumvents the major problems associated with conventional gene therapy in these disorders [1].
  • This negative autoregulatory action of GDF11 is strikingly like that of its homolog, GDF8/myostatin, in skeletal muscle, suggesting that similar strategies establish and maintain proper cell number during neural and muscular development [7].
  • Suppression of body fat accumulation in myostatin-deficient mice [2].

Biological context of Gdf8


Anatomical context of Gdf8


Associations of Gdf8 with chemical compounds

  • In each case, loss of Mstn led to a partial suppression of fat accumulation and of abnormal glucose metabolism [2].
  • To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA [13].
  • Genetic deletion of Myostatin, a member of the Transforming Growth Factor-beta family of signalling molecules, resulted in excessive growth of skeletal muscle [14].
  • To test the role of Myostatin in 3T3-L1 preadipocyte differentiation, we treated cultured 3T3-L1 preadipocytes with Myostatin dissolved in 0.1% trifluoroacetic acid (TFA) during differentiation after they had become confluent [15].
  • Incubation of C2C12 myotubes with graded doses of dexamethasone dose-dependently increased the intensity of nuclear myostatin immunostaining and also resulted in the appearance of cytoplasmic expression [16].

Physical interactions of Gdf8

  • We analysed the interaction kinetics of the two proteins and found that Follistatin binds Myostatin with a high affinity of 5.84 x 10(-10) M [17].
  • Here, we demonstrate that pharmacological blockade using a myostatin propeptide stabilized by fusion to IgG-Fc improved pathophysiology of the mdx mouse model of DMD [18].

Regulatory relationships of Gdf8


Other interactions of Gdf8

  • Consistent with this, the expression of dominant-negative Smad3 rescued the activity of a MyoD promoter-reporter in C(2)C(12) myoblasts treated with myostatin [3].
  • In this study we show that myostatin is an inhibitor of myoblast differentiation and that this inhibition is mediated through Smad 3 [3].
  • CONCLUSIONS.: Blocking the myostatin signal in mdx mice allowed the size of muscle fibers to increase, the fiber resistance to damage induced by exercise to increase, and the success of normal myoblast transplantation to improve [19].
  • The mature carboxyl-terminal domain encoded by Gdf11 is most closely related to Gdf8, being 90% identical to the mouse gene [23].
  • Myostatin levels were reduced in GC muscle of p27(-/-) mice (P<0.05) [24].

Analytical, diagnostic and therapeutic context of Gdf8


  1. Functional improvement of dystrophic muscle by myostatin blockade. Bogdanovich, S., Krag, T.O., Barton, E.R., Morris, L.D., Whittemore, L.A., Ahima, R.S., Khurana, T.S. Nature (2002) [Pubmed]
  2. Suppression of body fat accumulation in myostatin-deficient mice. McPherron, A.C., Lee, S.J. J. Clin. Invest. (2002) [Pubmed]
  3. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. Langley, B., Thomas, M., Bishop, A., Sharma, M., Gilmour, S., Kambadur, R. J. Biol. Chem. (2002) [Pubmed]
  4. Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition. Ohsawa, Y., Hagiwara, H., Nakatani, M., Yasue, A., Moriyama, K., Murakami, T., Tsuchida, K., Noji, S., Sunada, Y. J. Clin. Invest. (2006) [Pubmed]
  5. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Siriett, V., Salerno, M.S., Berry, C., Nicholas, G., Bower, R., Kambadur, R., Sharma, M. Mol. Ther. (2007) [Pubmed]
  6. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Clop, A., Marcq, F., Takeda, H., Pirottin, D., Tordoir, X., Bibé, B., Bouix, J., Caiment, F., Elsen, J.M., Eychenne, F., Larzul, C., Laville, E., Meish, F., Milenkovic, D., Tobin, J., Charlier, C., Georges, M. Nat. Genet. (2006) [Pubmed]
  7. Autoregulation of neurogenesis by GDF11. Wu, H.H., Ivkovic, S., Murray, R.C., Jaramillo, S., Lyons, K.M., Johnson, J.E., Calof, A.L. Neuron (2003) [Pubmed]
  8. Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Rebbapragada, A., Benchabane, H., Wrana, J.L., Celeste, A.J., Attisano, L. Mol. Cell. Biol. (2003) [Pubmed]
  9. Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice. McCroskery, S., Thomas, M., Platt, L., Hennebry, A., Nishimura, T., McLeay, L., Sharma, M., Kambadur, R. J. Cell. Sci. (2005) [Pubmed]
  10. Muscle-bone interactions in dystrophin-deficient and myostatin-deficient mice. Montgomery, E., Pennington, C., Isales, C.M., Hamrick, M.W. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2005) [Pubmed]
  11. Alterations of temporalis muscle contractile force and histological content from the myostatin and Mdx deficient mouse. Byron, C.D., Hamrick, M.W., Wingard, C.J. Arch. Oral Biol. (2006) [Pubmed]
  12. Myostatin-deficient mice lose more skeletal muscle mass than wild-type controls during hindlimb suspension. McMahon, C.D., Popovic, L., Oldham, J.M., Jeanplong, F., Smith, H.K., Kambadur, R., Sharma, M., Maxwell, L., Bass, J.J. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  13. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Reisz-Porszasz, S., Bhasin, S., Artaza, J.N., Shen, R., Sinha-Hikim, I., Hogue, A., Fielder, T.J., Gonzalez-Cadavid, N.F. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  14. The function of Myostatin and strategies of Myostatin blockade-new hope for therapies aimed at promoting growth of skeletal muscle. Patel, K., Amthor, H. Neuromuscul. Disord. (2005) [Pubmed]
  15. Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1 cultures. Kim, H.S., Liang, L., Dean, R.G., Hausman, D.B., Hartzell, D.L., Baile, C.A. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  16. Endogenous expression and localization of myostatin and its relation to myosin heavy chain distribution in C2C12 skeletal muscle cells. Artaza, J.N., Bhasin, S., Mallidis, C., Taylor, W., Ma, K., Gonzalez-Cadavid, N.F. J. Cell. Physiol. (2002) [Pubmed]
  17. Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis. Amthor, H., Nicholas, G., McKinnell, I., Kemp, C.F., Sharma, M., Kambadur, R., Patel, K. Dev. Biol. (2004) [Pubmed]
  18. Myostatin propeptide-mediated amelioration of dystrophic pathophysiology. Bogdanovich, S., Perkins, K.J., Krag, T.O., Whittemore, L.A., Khurana, T.S. FASEB J. (2005) [Pubmed]
  19. Improved success of myoblast transplantation in mdx mice by blocking the myostatin signal. Benabdallah, B.F., Bouchentouf, M., Tremblay, J.P. Transplantation (2005) [Pubmed]
  20. Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway is involved in myostatin-regulated differentiation repression. Yang, W., Chen, Y., Zhang, Y., Wang, X., Yang, N., Zhu, D. Cancer Res. (2006) [Pubmed]
  21. Myostatin negatively regulates satellite cell activation and self-renewal. McCroskery, S., Thomas, M., Maxwell, L., Sharma, M., Kambadur, R. J. Cell Biol. (2003) [Pubmed]
  22. Relationships between transforming growth factor-beta1, myostatin, and decorin: implications for skeletal muscle fibrosis. Zhu, J., Li, Y., Shen, W., Qiao, C., Ambrosio, F., Lavasani, M., Nozaki, M., Branca, M.F., Huard, J. J. Biol. Chem. (2007) [Pubmed]
  23. Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta superfamily during mouse embryogenesis. Nakashima, M., Toyono, T., Akamine, A., Joyner, A. Mech. Dev. (1999) [Pubmed]
  24. P27 knockout mice: reduced myostatin in muscle and altered adipogenesis. Lin, J., Della-Fera, M.A., Li, C., Page, K., Choi, Y.H., Hartzell, D.L., Baile, C.A. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD. Spiller, M.P., Kambadur, R., Jeanplong, F., Thomas, M., Martyn, J.K., Bass, J.J., Sharma, M. Mol. Cell. Biol. (2002) [Pubmed]
  26. Proteolytic processing of myostatin is auto-regulated during myogenesis. McFarlane, C., Langley, B., Thomas, M., Hennebry, A., Plummer, E., Nicholas, G., McMahon, C., Sharma, M., Kambadur, R. Dev. Biol. (2005) [Pubmed]
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