A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle.
Myostatin, which is a member of the TGF-beta superfamily, is a negative regulator of skeletal muscle formation. Double-muscled Piedmontese cattle have a C313Y mutation in myostatin and show increased skeletal muscle mass which resulted from an increase of myofiber number (hyperplasia) without that of myofiber size (hypertrophy). To examine whether this mutation in myostatin gene affects muscle development in a dominant negative manner, we generated transgenic mice overexpressing the mutated gene. The transgenic mice exhibited dramatic increases in the skeletal muscle mass resulting from hyperplasia without hypertrophy. In contrast, it has been reported that a myostatin mutated at its cleavage site produces hypertrophy without hyperplasia in the muscle. Thus, these results suggest that (1) the myostatin containing the missense mutation exhibits a dominant negative activity and that (2) there are two types in the dominant negative form of myostatin, causing either hypertrophy or hyperplasia.
Nishi
Masumi
M
Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minami-Jyosanjima cho, Tokushima 770-8506, Japan.
Yasue
Akihiro
A
Nishimatu
Shinichirou
S
Nohno
Tsutomu
T
Yamaoka
Takashi
T
Itakura
Mitsuo
M
Moriyama
Keiji
K
Ohuchi
Hideyo
H
Noji
Sumihare
S
D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D002645:Chickens; D017931:DNA Primers; D005260:Female; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology*; D006984:Hypertrophy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology*; D020125:Mutation, Missense; D018008:Myogenin / Q000235:genetics; D055435:Myostatin; D016133:Polymerase Chain Reaction; D012727:Sex Characteristics; D016212:Transforming Growth Factor beta / Q000235:genetics*
D017931:DNA Primers; C525912:Mstn protein, mouse; C503801:Myog protein, mouse; D018008:Myogenin; D055435:Myostatin; D016212:Transforming Growth Factor beta