title: Elimination of myostatin does not combat muscular dystrophy in dy mice but increases postnatal lethality.
abstract: Myostatin is a TGF-beta 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 dy(W) laminin alpha2-deficient and myostatin null mice. The resulting double-deficient dy(W)/dy(W);Mstn(-/-) mice had a severe clinical phenotype similar to that of dy(W)/dy(W) mice, even though muscle regeneration was increased. Degeneration and inflammation of muscle were not alleviated. The pre-weaning mortality of dy(W)/dy(W);Mstn(-/-) mice was increased compared to dy(W)/dy(W), 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.
authors.affiliation: The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Li
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Eva
authors.initials: E
authors.lastname: Engvall
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005838:Genotype; D007797:Laminin / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000378:metabolism; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D055435:Myostatin; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000737:chemistry*
chemical_list: D007797:Laminin; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta; C102645:laminin alpha 2