Atlantic salmon myostatin: Characterization of the promoter and the activin IIB receptor

Myostatin is a negative regulator of skeletal muscle growth and belongs to the TGF-β superfamily of growth and differentiation factors. Myostatin functions by inhibiting myoblast proliferation and differentiation (Thomas, 2000; Rios, 2001; Taylor, 2001; Langley, 2000). Mutations in the myostatin gene are found in cattle such as Belgian Blue and Piedmontese (McPerron et al, 1997;Kambadur, 1997; McPerron and Lee, 1997) with the “double muscled” phenotype, and recently in a human child (Schuelke, 2004). Myostatin encoding sequences have been analysed in a large number of species and is remarkably well conserved throughout evolution. The myostatin sequence is cloned and studied in Atlantic salmon (Salmo salar), and is found to exist in two copies (Østbye et al, 2001). In most vertebrates only a single myostatin gene is reported, and this is almost exclusive expressed in skeletal muscle. The two myostatin genes of Atlantic salmon are expressed in a wide range of tissues. Myostatin show many characteristics in common with other members of the TGFβ superfamily. The predicted myostatin protein sequence has a putative Nterminal signal sequence for secretion, a RXXR proteolytic processing site, and a C-termial domain following the processing site, which contains nine cysteine residues with the characteristic spacing (McPerron and Lee, 1997). Proteolysis of myostatin gives rise to a N-terminal propeptide and a C-terminal mature myostatin. Dimers of the mature myostatin and the propeptide remain noncovalently associated after cleavage.