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Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member

Naturevolume 387pages8390 (1997) | Download Citation

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Abstract

The transforming growth factor-β (TGF-β) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals1. Using degenerate polymerase chain reaction, we have identified a new murine TGF-β 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.

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Affiliations

  1. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • Alexandra C. McPherron
    •  & Se-Jin Lee
  2. Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • Ann M. Lawler

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https://doi.org/10.1038/387083a0

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