Positional cloning and genetic engineering of the myostatin gene causing double muscling in cattle

Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double-muscling, namely myostatin, and causal loss-of-function mutations therein. Myostatin is a novel member of the TGF-beta superfamily of growth and differentiation factors. Using conditional gene targeting in a murine model, we have demonstrated that post-natal muscle specific inactivation of the myostatin gene causes full-blown double muscling. This demonstrates the potential value of myostatin antagonist whether to promote muscle regeneration in patients suffering from muscle wasting disease, or to enhance meat production in livestock species. Finally, by targeting a myostatin transinhibitor on the Y chromosome, we have demonstrated in the mouse the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows.