McPherron A C, Lee S J
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12457-61. doi: 10.1073/pnas.94.23.12457.
Myostatin (GDF-8) is a member of the transforming growth factor beta 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.
肌肉生长抑制素（GDF - 8）是分泌型生长和分化因子转化生长因子β超家族的成员，对小鼠骨骼肌质量的正常调节至关重要。在此，我们报告了其他9种脊椎动物的肌肉生长抑制素序列，并鉴定了两种双肌牛品种（比利时蓝牛和皮埃蒙特牛）中牛肌肉生长抑制素编码序列的突变，已知这两个品种相对于普通牛肌肉量有所增加。比利时蓝牛的肌肉生长抑制素序列在第三外显子中有一个11个核苷酸的缺失，导致移码突变，几乎消除了该分子所有成熟的活性区域。皮埃蒙特牛的肌肉生长抑制素序列在第3外显子中有一个错义突变，导致该蛋白成熟区域中一个不变的半胱氨酸被酪氨酸取代。双肌牛和肌肉生长抑制素基因敲除小鼠的表型相似，这表明肌肉生长抑制素在这两个物种中发挥相同的生物学功能，并且是其他农场动物基因操作的潜在有用靶点。
