A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle

Abstract

An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled animals are characterized by an increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia-that is, an increase in the number of muscle fibers rather than in their individual diameter. Although the hereditary nature of the double-muscled condition was recognized early on, the precise mode of inheritance has remained controversial; monogenic (domainant and recessive), oligogenic and polygenic models have been proposed. In the Belgian Blue cattle breed (BBCB), segregation analysis performed both in experimental crosses and in the outbred population suggested an autosomal recessive inheritance. This was confirmed when the muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on the centromeric end of bovine chromosome 2 (ref. 5). We used a positional candidate approach to demonstrate that a mutation in bovine MSTN, which encodes myostatin, a member of the TGF beta superfamily, is responsible for the double-muscled phenotype. We report an 11-bp deletion in the coding sequence for the bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle.

Evidence for placental compensation in cattle

“…Dam and calf size The hypermuscularity in the BB breed originates from an increase in skeletal muscle fibers, caused by a mutation and associated inactivation of the myostatin (mh) gene (Grobet et al, 1997). As the inactivation of the mh-gene is already present during intrauterine development, BB calves are extremely muscled at birth, giving rise to high birth weights as recorded in the present and previous studies (Kolkman et al, 2010).…”

The myostatin null mutation and clenbuterol administration elicit additive effects in mice

“…However, with identification of Mstn and its association to the wellcharacterized double-muscling phenotype in cattle (Grobet et al, 1997;Kambadur et al, 1997;, the idea of a muscle chalone -an inhibitory molecule secreted by the muscle, which ultimately governed its size (Bullough, 1962 and1965) -was revived (Lee and McPherron, 1999). If Mstn was this muscle chalone, the loss of its function to regulate the size of muscle independent of other factors would allow muscle to grow to its maximal possible size.…”

“…Another strategy to alter animal growth is to introduce mutations into the Mstn gene as occurs naturally in double-muscled cattle. These cattle exhibit striking increases in muscle growth and reductions in fat mass (Grobet et al, 1997;Kambadur et al, 1997;Grobet et al, 1998). Transgenic Mstn null mice can be used as a model for this effect as this species also exhibits increased muscularity and decreased fat deposition McPherron and Lee, 2002).…”

MicroRNA-27a promotes porcine myoblast proliferation by downregulating myostatin expression

“…The complete CDS of myostatin has been cloned from swine (Ji et al, 1998), cattle (Grobet et al, 1997), horse (Hosoyama et al, 2002) and sheep (Sharma et al, 1999). MiRNAs negatively regulate gene expression at the posttranscriptional level via binding to the 3'UTR of target mRNAs (Bartel, 2004;Tanzer and Stadler, 2004;de Moor et al, 2005;Gladka et al, 2012).…”