s is likely to cause the muscular phenotype of this breed of sheep.
Structure and mechanism of action
Myostatin is a member of the TGF beta superfamily of proteins.
Human myostatin consists of two identical subunits, each consisting of 109 (NCBI database claims human myostatin is 375 residues long) amino acid residues. Its total molecular weight is 25.0 kDa. The protein is made in an inactive form. For it to be activated, a protease cleaves the NH2-terminal, or "pro-domain" portion of the molecule, resulting in the now-active COOH-terminal dimer.
Myostatin binds to the activin type II receptor, resulting in a recruitment of a coreceptor called Alk-3 or Alk-4. This coreceptor then initiates a cell signaling cascade in the muscle, which includes the activation of transcription factors in the SMAD family - SMAD2 and SMAD3. These factors then induce myostatin-specific gene regulation. When applied to myoblasts, myostatin inhibits their differentiation into mature muscle fibers.
Recently, myostatin has also been shown to inhibit Akt, a kinase that is sufficient to cause muscle hypertrophy, in part through the activation of protein synthesis. However, it is notable that Akt does not responsible for all of the observed muscle hyperthrophic effects which are mediated by myostatin inhibition
Myostatin is also classed as a myokine, and is in fact considered the first myokine to have been characterized.
Effects in animals
Double muscled cattle
After that discovery, several laboratories cloned and established the nucleotide sequence of a myostatin gene in two breeds of cattle Belgian Blue and Piedmontese, and found that these animals have mutations in that myostatin gene (various mutations in each breed) which in one way or another lead to absence of functional myostatin. Unlike mice with a damaged myostatin gene, in these cattle breeds the muscle cells multiply rather than enlarge. People describe these cattle breeds as "double muscled", but the total increase in all muscles is no more than 40%.
Animals lacking myostatin or animals treated with substances such as follistatin that block the binding of myostatin to its receptor have significantly larger muscles. Thus, reduction of myostatin could potentially benefit the livestock industry, with even a 20 percent reduction in myostatin levels potentially having a large effect on the development of muscles.
However, the animal breeds developed as homozygous for myostatin deficiency have reproduction issues due to their unusually heavy and bulky offspring, and require special care and a more expensive diet to achieve a superior yield. This negatively affects economics of myostatin-deficient breeds to the point where they do not usually offer an obvious advantage. While hypertrophic meat (e.g. from Piedmontese beef) has a place on the specialist market due to its unusual properties, at least for purebred myostatin-deficient strains the expenses and (especially in cattle) necessity of veterinary supervision place them at a disadvantage in the bulk market.
Performance enhancement in dogs
A 2007 NIH study in PLOS Genetics found a significant relationship in whippets between a myostatin mutation and racing performance. Whippets that were heterozygous for a 2 base pair deletion in the myostatin gene were significantly over-represented in the top racing classes. The mutation resulted in a truncated myostatin protein, likely resulting in an inactive form of myostatin.
Whippets with a homozygous deletion were apparently less able runners although their overall appearance was significantly more muscular. Whippets with the homozygous deletion also had an unusual body shape, with a broader head, pronounced overbite, shorter legs, and thicker tails. These whippets have also been called "bully whippets" by the breeding community due to their size. Despite the name "bully", these dogs tend to have a friendly and positive demeanour towards people as usual for whippets.
This particular mutation was not found in other muscular dog breeds such as boxers and mastiffs, nor was it found in other sighthounds 