title: Overexpression of the dominant-negative form of myostatin results in doubling of muscle-fiber number in transgenic medaka (Oryzias latipes).
abstract: In addition to altering the phenotypes of gene-modified animals, transgenesis also has the potential to facilitate access to the various mechanisms underlying the development and functioning of specific phenotypes and genes, respectively. Myostatin (MSTN) is implicated in double-muscling when mutated in mammals, indicating that MSTN is a negative regulator of skeletal muscle formation. In order to elucidate the role of an MSTN equivalent in fish muscle formation, we created a transgenic medaka strain that expresses dominant-negative MSTN exclusively in skeletal muscle, d-rR-Tg(OlMA1-C315Y-MSTN-hrGFPII-FLAG). The transgenic fish exhibited increased production of skeletal muscle fibers at the adult stage (hyperplasia), although gross muscle mass was not altered. During embryogenesis, ectopic accumulation and misalignment of muscle fibers, possibly due to muscle-fiber hypertrophy, were observed in the transgenic medaka. Our findings suggest that MSTN function is required for regulating the appropriate growth of skeletal muscle in medaka. Unlike in mammals, MSTN loss-of-function failed to induce double-muscling in medaka, despite the highly conserved nature of MSTN function among taxa.
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sawatari
authors.forename: Ryoko
authors.initials: R
authors.lastname: Seki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Adachi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Uji
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wakamatsu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakata
authors.forename: Masato
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006965:Hyperplasia; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D009154:Mutation; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D009990:Oryzias / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D029941:Fish Proteins; D055435:Myostatin