title: Overexpression of follistatin in trout stimulates increased muscling.
abstract: Deletion or inhibition of myostatin in mammals has been demonstrated to markedly increase muscle mass by hyperplasia, hypertrophy, or a combination of both. Despite a remarkably high degree of conservation with the mammalian protein, the function of myostatin remains unknown in fish, many species of which continue muscle growth throughout the lifecycle by hyperplasia. Transgenic rainbow trout (Oncorhynchus mykiss) overexpressing follistatin, one of the more efficacious antagonists of myostatin, were produced to investigate the effect of this protein on muscle development and growth. P(1) transgenics overexpressing follistatin in muscle tissue exhibited increased epaxial and hypaxial muscling similar to that observed in double-muscled cattle and myostatin null mice. The hypaxial muscling generated a phenotype reminiscent of well-developed rectus abdominus and intercostal muscles in humans and was dubbed "six pack." Body conformation of the transgenic animals was markedly altered, as measured by condition factor, and total muscle surface area increased. The increased muscling was due almost exclusively to hyperplasia as evidenced by a higher number of fibers per unit area and increases in the percentage of smaller fibers and the number of total fibers. In several individuals, asymmetrical muscling was observed, but no changes in mobility or behavior of follistatin fish were observed. The findings indicate that overexpression of follistatin in trout, a species with indeterminate growth rate, enhances muscle growth. It remains to be determined whether the double muscling in trout is due to inhibition of myostatin, other growth factors, or both.
authors.affiliation: Department of Fisheries, Animal and Veterinary Science, University of Rhode Island, Kingston, Rhode Island 02881, USA.
authors.forename: Erika F
authors.initials: EF
authors.lastname: Medeiros
authors.forename: Michael P
authors.initials: MP
authors.lastname: Phelps
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Fuentes
authors.forename: Terence M
authors.initials: TM
authors.lastname: Bradley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D038681:Follistatin / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D008297:Male; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype
chemical_list: D029941:Fish Proteins; D038681:Follistatin; D055435:Myostatin