Myostatin

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Myostatin
Other names:	GDF-8, Myostatin
Genetic data
Locus:	Chr. 2 q32.1
Gene code:	HUGO: GDF8
Protein Structure/Function
Protein type:	TGF beta superfamily
Functions:	Negative regulator of skeletal muscle growth
Domains:	TGFβ domain
Other
Taxa expressing:	Homo sapiens; homologs: many metazoan phyla
Cell types:	many, skeletal muscle
Subcellular localization:	Extracellular
Medical/Biotechnological data
Diseases:	Muscle hypertrophy
Database Links
Entrez:	2660
OMIM:	601788
RefSeq:	NM_005259
UniProt:	O14793

Myostatin (formerly known as Growth differentiation factor 8) is a growth factor that limits muscle tissue growth, i.e. higher concentrations of myostatin in the body cause the individual to have less developed muscles. The myostatin protein is produced in skeletal muscle cells, circulates in the blood and acts on muscle tissue, apparently by slowing down the development of muscle stem cells. The precise mechanism remains unknown.

Contents 1 Discovery and sequencing 2 Effects of inactivated myostatin 3 Biochemistry 4 Potential clinical significance 5 See also 6 References 7 External links

[edit] Discovery and sequencing

Myostatin and the associated gene were discovered in 1997 by geneticists McPherron and Se-Jin Lee, who also produced a strain of mutant mice that lack the gene and are about twice as strong as normal mice.^[1] The gene has been sequenced in humans, mice, zebrafish and several other animals, showing few differences among species.

[edit] Effects of inactivated myostatin

Lee found in 1997 that the strong Belgian Blue and Piedmontese cattle strains have a defective myostatin gene; these strains have been produced through breeding. ^[2][3][4]

In 2001, Lee created mice with intact myostatin gene and large muscle mass by inserting mutations that boosted the production of various myostatin blocking substances. This work led to the usage of the moniker "mighty mice."

In 2004, a German boy was diagnosed with a mutation in both copies of the myostatin-producing gene, making him considerably stronger than his peers. His mother, a former sprinter, has a mutation in one copy of the gene.^{[5][6][7][8][9][10]}

[edit] Biochemistry

Myostatin is a member of the TGF-beta superfamily of proteins.

Human Myostatin consists of two identical subunits, each consisting of 110 amino acid residues. Its total molecular weight is 25.0 kDa. It can be produced in genetically engineered E. coli and is available for sale.

[edit] Potential clinical significance

Further research into myostatin and the myostatin gene may lead to therapies for muscular dystrophy.^[11] The idea is to introduce substances that block myostatin. In 2002, researchers at the University of Pennsylvania showed that monoclonal antibody specific to myostatin improves the condition of mice with muscular dystrophy, presumably by blocking myostatin's action.

In 2005, Lee showed that a two-week treatment of normal mice with soluble activin type IIB receptor, a molecule that is normally attached to cells and binds to myostatin, leads to a significantly increased muscle mass (up to 60%).^[12] It is thought that binding of myostatin to the soluble activin receptor prevents it from interacting with the cell-bound receptors.

It remains unclear whether long term treatment of muscular dystropy with myostatin inhibitors is beneficial: the depletion of muscle stem cells could worsen the disease later on.

As of 2005, no myostatin inhibiting drugs for humans are on the market, but an antibody genetically engineered to neutralize myostatin was developed by New Jersey pharmaceutical company Wyeth.^[13] The inhibor is called MYO-029 and recently underwent testing however the results have not yet been made public.^[14][15][16] Some athletes, eager to get their hands on such drugs, turn to the internet, where fake "myostatin blockers" are being sold.

Johns Hopkins University owns the patents on myostatin.

[edit] See also

• Facioscapulohumeral muscular dystrophy
• Wyeth
• Muscular Dystrophy Association

[edit] References

1. ^ McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997;387:83-90. PMID 9139826.
2. ^ Photos of double muscled Myostatin inhibited Belgian Blue Bulls
3. ^ Kambadur R, Sharma M, Smith T, Bass J (1997). "Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle". Genome Res 7 (9): 910-6. PMID 9314496. 
4. ^ McPherron A, Lee S (1997). "Double muscling in cattle due to mutations in the myostatin gene". Proc Natl Acad Sci U S A 94 (23): 12457-61. PMID 9356471. 
5. ^ cevgenetica: Gene Mutation Makes German Boy Extra Strong Muscle Baby
6. ^ Gina Kolota: A Very Muscular Baby Offers Hope Against Diseases, The New York Times, June 24, 2004. (Requires login)
7. ^ Genetic mutation turns tot into superboy
8. ^ Muscle Boy
9. ^ One Strong Tyke: Gene mutation in muscular boy may hold disease clues
10. ^ Schuelke M, Wagner K, Stolz L, Hübner C, Riebel T, Kömen W, Braun T, Tobin J, Lee S (2004). "Myostatin mutation associated with gross muscle hypertrophy in a child". N Engl J Med 350 (26): 2682-8. PMID 15215484. 
11. ^ Kate Ruder: Strong Boy Could Benefit Research on Muscular Dystrophy, Genome News Network, June 24, 2004.
12. ^ Lee SJ et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci U S A. Dec 5, 2005. PMID 16330774
13. ^ 2/23/05 Wyeth MYO-029 press release
14. ^ FDA's record on the MYO-029 Myostatin Inhibor Trial is NCT00104078
15. ^ Medical News Today press article about the Myostatin Inhibtor trial
16. ^ http://www.mda.org/research/061204myo_029_nov06.html

[edit] External links

• Elzi Volk: The Myostatin Gene
• MDA article on the Myostatin findings
• NPR.org: Myostatin Therapies Hold Hope for Muscle Diseases by Jon Hamilton