¹Généthon, CNRS UMR8115, Evry, France

Correspondence: Dr I Richard, Généthon, CNRS UMR8115, 1 rue de l'internationale, 91000 Evry, France. E-mail: richard@genethon.fr

²These authors contributed equally to this work.

Received 3 August 2006; Revised 3 October 2006; Accepted 20 December 2006; Published online 1 March 2007.

Abstract

Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different strategies has proved beneficial for the pathophysiology of the dystrophin-deficient mdx mouse. In this report, we tested the inhibition of myostatin by AAV-mediated expression of a mutated propeptide in animal models of two limb-girdle muscular dystrophies: LGMD2A caused by mutations in the calpain 3 (CAPN3) gene and LGMD2D caused by mutations in the -sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the -sarcoglycan-deficient muscle fibers did not improve after transfer of the myostatin propeptide. In calpain 3-deficient mice, a boost in muscle mass and an increase in absolute force were obtained, suggesting that myostatin inhibition could constitute a therapeutic strategy in this predominantly atrophic disorder.