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: Masumi Nishi, Akihiro Yasue, Shinichirou Nishimatu, Tsutomu Nohno, Takashi Yamaoka, Mitsuo Itakura, Keiji Moriyama, Hideyo Ohuchi, Sumihare Noji
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 293 Issue 1 Pg. 247-51 (Apr 26 2002) ISSN: 0006-291X [Print] United States
• PMID: 12054591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Mstn protein, mouse
• Myog protein, mouse
• Myogenin
• Myostatin
• Transforming Growth Factor beta

Topics

• Amino Acid Substitution
• Animals
• Cattle
• Chickens
• DNA Primers
• Female
• Hyperplasia (genetics, pathology)
• Hypertrophy
• Male
• Mice
• Mice, Transgenic
• Muscle, Skeletal (pathology)
• Mutation, Missense
• Myogenin (genetics)
• Myostatin
• Polymerase Chain Reaction
• Sex Characteristics
• Transforming Growth Factor beta (genetics)