Elimination of Myostatin Does Not Combat Muscular Dystrophy in dy Mice but Increases Postnatal Lethality

Myostatin is a TGF-β family member and a negative regulator of skeletal muscle growth. It has been proposed that reduction or elimination of myostatin could be a treatment for degenerative muscle diseases such as muscular dystrophy. Laminin-deficient congenital muscular dystrophy is one of the most severe forms of muscular dystrophy. To test the possibility of ameliorating the dystrophic phenotype in laminin deficiency by eliminating myostatin, we crossed dyW laminin α2-deficient and myostatin null mice. The resulting double-deficient dyW/dyW;Mstn−/− mice had a severe clinical phenotype similar to that of dyW/dyW mice, even though muscle regeneration was increased. Degeneration and inflammation of muscle were not alleviated. The pre-weaning mortality of dyW/dyW;Mstn−/− mice was increased compared to dyW/dyW, most likely due to significantly less brown and white fat in the absence of myostatin, and postweaning mortality was not significantly improved. These results show that eliminating myostatin in laminin-deficiency promotes muscle formation, but at the expense of fat formation, and does not reduce muscle pathology. Any future therapy based on myostatin may have undesirable side effects.