Everything about Myostatin totally explained
Myostatin (formerly known as
Growth differentiation factor 8) is a
growth factor that limits
muscle tissue growth, for example higher concentrations of myostatin in the body may cause the individual to have less developed muscles.
The myostatin
protein is produced primarily in skeletal muscle
cells, circulates in the blood and lymph and acts on muscle tissue, apparently by slowing down the development of muscle
stem cells. The precise mechanism remains unknown. Its functions in non-mammalian vertebrates appear to be somewhat conserved as muscle-specific actions have been demonstrated in birds. However, it's produced in many different fish tissues, suggesting that it may regulate more than just muscle mass in these vertebrates.
Discovery and sequencing
Myostatin and the associated
gene were discovered in 1997 by geneticists Alexandra McPherron and Se-Jin Lee, who also produced a strain of mutant
mice that lack the gene and have about twice as much muscle as normal mice. These mice were subsequently named "mighty mice". The gene has been sequenced in
humans, mice, several other mammals and many different fish species, most of which are current or potential cultivars. The primary coding sequence is highly conserved among all vertebrates as is the genomic organization . These and other recent studies also indicate that the myostatin gene in fish has been duplicated as most fish species possess two distinct myostatin genes (MSTN-1 & -2) while
salmonids have four (MSTN-1a, -1b, -2a & -2b) This further suggests that the physiological and developmental aspects of myostatin biology may be quite different from that in mammals.
Effects of inactivated myostatin
Lee and others found in 1997 that the double muscled cattle breeds
Belgian Blue and
Piedmontese have defective myostatin genes; these strains have been produced through breeding.
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. More recently, an American boy born 2005 was diagnosed with the same condition.
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 k
Da. It can be produced in genetically engineered
E. coli or eukaryotic cells and the recombinant protein from both sources is commercially available. However, due to the unique manner by which the mature protein is processed, there's considerable doubt as to the effectiveness of myostatin generated in E. coli.
Performance Enhancement in Dogs
A 2007 NIH study in PLOS Genetics 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's normally attached to cells and binds to myostatin, leads to a significantly increased muscle mass (up to 60%). 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. The inhibitor is called
MYO-029 and recently underwent testing however the results have not yet been made public. 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.
Further Information
Get more info on 'Myostatin'.
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