title: Myostatin-deficient medaka exhibit a double-muscling phenotype with hyperplasia and hypertrophy, which occur sequentially during post-hatch development.
abstract: Myostatin (MSTN) functions as a negative regulator of skeletal muscle mass. In mammals, MSTN-deficient animals result in an increase of skeletal muscle mass with both hyperplasia and hypertrophy. A MSTN gene is highly conserved within the fish species, allowing speculation that MSTN-deficient fish could exhibit a double-muscled phenotype. Some strategies for blocking or knocking down MSTN in adult fish have been already performed; however, these fish show either only hyperplastic or hypertrophic growth in muscle fiber. Therefore, the role of MSTN in fish myogenesis during post-hatch growth remains unclear. To address this question, we have made MSTN-deficient medaka (mstnC315Y) by using the targeting induced local lesions in a genome method. mstnC315Y can reproduce and have the same survival period as WT medaka. Growth rates of WT and mstnC315Y were measured at juvenile (1-2wk post-hatching), post-juvenile (3-7wk post-hatching) and adult (8-16wk post-hatching) stages. In addition, effects of MSTN on skeletal muscle differentiation were investigated at histological and molecular levels at each developmental stage. As a result, mstnC315Y show a significant increase in body weight from the post-juvenile to adult stage. Hyper-morphogenesis of skeletal muscle in mstnC315Y was accomplished due to hyperplastic growth from post-juvenile to early adult stage, followed by hypertrophic growth in the adult stage. Myf-5 and MyoD were up-regulated in mstnC315Y at the hyperplastic growth phase, while myogenin was highly expressed in mstnC315Y at the hypertrophic growth phase. These indicated that MSTN in medaka plays a dual role for muscle fiber development. In conclusion, MSTN in medaka regulates the number and size of muscle fiber in a temporally-controlled manner during posthatch growth.
authors.affiliation: Aquatic Animal Health Division, National Research Institute of Aquaculture, Fisheries Research Agency, 224-1 Hiruta, Tamaki, Mie, 519-0423, Japan. Electronic address: chisada@affrc.go.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Chisada
authors.affiliation: Aquaculture Biology Division, National Research Institute of Aquaculture, Fisheries Research Agency, 224-1 Hiruta, Tamaki, Mie, 519-0423, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Center for Novel Science Initiatives, National Institutes of Natural Sciences, 4-3-13 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kimori
authors.affiliation: Sequence Technology Team, RIKEN Genomic Sciences Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.affiliation: Sequence Technology Team, RIKEN Genomic Sciences Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.affiliation: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Aquatic Animal Health Division, National Research Institute of Aquaculture, Fisheries Research Agency, 224-1 Hiruta, Tamaki, Mie, 519-0423, Japan. Electronic address: yoshiura@fra.affrc.go.jp.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Yoshiura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D003001:Cloning, Molecular; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006965:Hyperplasia; D006984:Hypertrophy; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D055435:Myostatin / Q000235:genetics*; D009990:Oryzias / Q000235:genetics / Q000254:growth & development*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D055435:Myostatin