title: A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle.
abstract: 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.
authors.affiliation: Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minami-Jyosanjima cho, Tokushima 770-8506, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Nishi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yasue
authors.forename: Shinichirou
authors.initials: S
authors.lastname: Nishimatu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Hideyo
authors.initials: H
authors.lastname: Ohuchi
authors.forename: Sumihare
authors.initials: S
authors.lastname: Noji
mesh_terms: 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*
chemical_list: D017931:DNA Primers; C525912:Mstn protein, mouse; C503801:Myog protein, mouse; D018008:Myogenin; D055435:Myostatin; D016212:Transforming Growth Factor beta