TY - JOUR
T1 - Overexpression of the dominant-negative form of myostatin results in doubling of muscle-fiber number in transgenic medaka (Oryzias latipes)
AU - Sawatari, Etsuko
AU - Seki, Ryoko
AU - Adachi, Tomoko
AU - Hashimoto, Hisashi
AU - Uji, Susumu
AU - Wakamatsu, Yuko
AU - Nakata, Takahiro
AU - Kinoshita, Masato
N1 - Funding Information:
This work was supported by the Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN), Japan .
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cbpa.2009.10.030
DO - 10.1016/j.cbpa.2009.10.030
M3 - Article
C2 - 19883781
AN - SCOPUS:72049131558
VL - 155
SP - 183
EP - 189
JO - Comparative biochemistry and physiology. Part A, Molecular & integrative physiology
JF - Comparative biochemistry and physiology. Part A, Molecular & integrative physiology
SN - 1095-6433
IS - 2
ER -