Identification of the double-muscling gene

Belgian Blue Cattle are characterized by an exceptional muscular hypertrophy commonly referred to as “double-muscling”.   In the eighties, Prof. Hanset (ULiège) demonstrated that this phenotype involved a major gene.  We confirmed this by first mapping and then cloning the causal gene which turned out to be an autocrine negative regulator of muscle growth baptized myostatin (MSTN) by S.J. Lee.  We subsequently showed that all double-muscled cattle are homozygous or compound heterozygous for an allelic series of at least seven MSTN loss-of-function mutations.  We went further to show in conditional KO mice that post-natal inactivation of MSTN still causes an increase in muscle mass (thus suggesting the possibility to treat sarcopenia or increase carcass yield with MSTN inhibitors), and to show the feasibility of making male-specific double-muscling by knocking constructs encoding MSTN inhibitor in the Y chromosome (a very interesting economic proposition). 

Key publications

A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Grobet L, Martin LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J, Schoeberlein A, Dunner S, Ménissier F, Massabanda J, Fries R, Hanset R, Georges MNat Genet 17:71-74 (1997).

Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle. Grobet L, Poncelet D, Royo LJ, Brouwers B, Pirottin D, Michaux C, Ménissier F, Zanotti M, Dunner S, Georges MMamm Genome 9:210-213 (1998).

Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene. Grobet L, Pirottin D, Farnir F, Poncelet D, Royo LJ, Brouwers B, Christians E, Desmecht D, Coignoul F, Kahn R, Georges M. Genesis 35:227-238 (2003).

Transgenic engineering of male-specific muscular hypertrophy. Pirottin D, Grobet L, Adamantidis A, Farnir F, Herens C, Schrøder HD, Georges MProc Natl Acad Sci U S A 102:6413-6418 (2005).

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