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PMID:9139826

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Citation

McPherron, AC, Lawler, AM and Lee, SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83-90

Abstract

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.

Links

PubMed Online version:10.1038/387083a0

Keywords

Aging/metabolism; Amino Acid Sequence; Animals; Body Weight/genetics; Body Weight/physiology; CHO Cells; Cloning, Molecular; Cricetinae; Embryo, Mammalian/metabolism; Gene Targeting; Homozygote; Humans; Hyperplasia/genetics; Hypertrophy/genetics; In Situ Hybridization; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Muscle, Skeletal/pathology; Muscle, Skeletal/physiology; Myostatin; Polymerase Chain Reaction; Protein Sorting Signals/genetics; Stem Cells; Transforming Growth Factor beta/chemistry; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GDF8

involved_in

GO:0048632: negative regulation of skeletal muscle tissue growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GDF8

GO:0048632: negative regulation of skeletal muscle tissue growth

ECO:0000315:

P

Fig 4a-d; disruption of GDF-8's normal functioning

complete
CACAO 2282


See also

References

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