Myostatin (GDF-8) is a member of the transforming growth factor β superfamily of secreted growth and differentiation factors that is essential for proper regulation of skeletal muscle mass in mice. Here we report the myostatin sequences of nine other vertebrate species and the identification of mutations in the coding sequence of bovine myostatin in two breeds of double-muscled cattle, Belgian Blue and Piedmontese, which are known to have an increase in muscle mass relative to conventional cattle. The Belgian Blue myostatin sequence contains an 11-nucleotide deletion in the third exon which causes a frameshift that eliminates virtually all of the mature, active region of the molecule. The Piedmontese myostatin sequence contains a missense mutation in exon 3, resulting in a substitution of tyrosine for an invariant cysteine in the mature region of the protein. The similarity in phenotypes of double-muscled cattle and myostatin null mice suggests that myostatin performs the same biological function in these two species and is a potentially useful target for genetic manipulation in other farm animals.
The transforming growth factor β superfamily encompasses a large group of secreted growth and differentiation factors that play important roles in regulating development and tissue homeostasis (1). We have recently described a member of this family, myostatin, that is expressed specifically in developing and adult skeletal muscle and functions as a negative regulator of skeletal muscle mass in mice (2). Myostatin null mice generated by gene targeting show a dramatic and widespread increase in skeletal muscle mass. Individual muscles in myostatin null mice weigh 2- to 3-fold more than those of wild-type mice, primarily due to an increased number of muscle fibers without a corresponding increase in the amount of fat. To pursue potential therapeutic and agricultural applications of increasing muscle mass by inhibition of myostatin activity, we have been characterizing myostatin in animals other than mice. Here we report that the myostatin gene is highly conserved among vertebrate species and that two breeds of cattle that are characterized by increased muscle mass (double muscling), Belgian Blue (3) and Piedmontese (4), have mutations in the myostatin coding sequence. These results demonstrate that the function of myostatin has been highly conserved among vertebrates. hope it helps
