Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member.
The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.
McPherron
A C
AC
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Lawler
A M
AM
Lee
S J
SJ
D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000378:metabolism; D018390:Gene Targeting; D006720:Homozygote; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D006984:Hypertrophy / Q000235:genetics; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D055435:Myostatin; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics; D013234:Stem Cells; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D021382:Protein Sorting Signals; D016212:Transforming Growth Factor beta