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

Author

Listed:
  • Alexandra C. McPherron

    (Johns Hopkins University School of Medicine)

  • Ann M. Lawler

    (Johns Hopkins University School of Medicine)

  • Se-Jin Lee

    (Johns Hopkins University School of Medicine)

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.

Suggested Citation

  • Alexandra C. McPherron & Ann M. Lawler & Se-Jin Lee, 1997. "Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member," Nature, Nature, vol. 387(6628), pages 83-90, May.
    • Handle: RePEc:nat:nature:v:387:y:1997:i:6628:d:10.1038_387083a0
    DOI: 10.1038/387083a0
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    1. Jennifer M. Petrosino & Scott A. Hinger & Volha A. Golubeva & Juan M. Barajas & Lisa E. Dorn & Chitra C. Iyer & Hui-Lung Sun & W. David Arnold & Chuan He & Federica Accornero, 2022. "The m6A methyltransferase METTL3 regulates muscle maintenance and growth in mice," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Flavia A. Graca & Mamta Rai & Liam C. Hunt & Anna Stephan & Yong-Dong Wang & Brittney Gordon & Ruishan Wang & Giovanni Quarato & Beisi Xu & Yiping Fan & Myriam Labelle & Fabio Demontis, 2022. "The myokine Fibcd1 is an endogenous determinant of myofiber size and mitigates cancer-induced myofiber atrophy," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. X.P. An & J.G. Wang & J.X. Hou & H.B. Zhao & L. Bai & G. Li & L.X. Wang & X.Q. Liu & W.P. Xiao & Y.X. Song & B.Y. Cao, 2011. "Polymorphism identification in the goat MSTN gene and association analysis with growth traits," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 56(12), pages 529-535.
    4. Marco Thürkauf & Shuo Lin & Filippo Oliveri & Dirk Grimm & Randall J. Platt & Markus A. Rüegg, 2023. "Fast, multiplexable and efficient somatic gene deletions in adult mouse skeletal muscle fibers using AAV-CRISPR/Cas9," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Jooyoung Kim & Kwanghoon Park & Joohyung Lee, 2020. "Myostatin A55T Genotype is Associated with Strength Recovery Following Exercise-Induced Muscle Damage," IJERPH, MDPI, vol. 17(13), pages 1-8, July.
    6. Katsuhiko Suzuki & Amir Hossein Ahmadi Hekmatikar & Shadi Jalalian & Shaghayegh Abbasi & Elmira Ahmadi & Abdolreza Kazemi & Ruheea Taskin Ruhee & Kayvan Khoramipour, 2022. "The Potential of Exerkines in Women’s COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise," IJERPH, MDPI, vol. 19(23), pages 1-21, November.
    7. Chuanyan Wu & Yan Borné & Rui Gao & Maykel López Rodriguez & William C. Roell & Jonathan M. Wilson & Ajit Regmi & Cheng Luan & Dina Mansour Aly & Andreas Peter & Jürgen Machann & Harald Staiger & Andr, 2021. "Elevated circulating follistatin associates with an increased risk of type 2 diabetes," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    8. Remigiusz Domin & Daniela Dadej & Michał Pytka & Ariadna Zybek-Kocik & Marek Ruchała & Przemysław Guzik, 2021. "Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People," IJERPH, MDPI, vol. 18(3), pages 1-36, January.
    9. Hanfang Bi & Shanshan Xie & Chunbo Cai & Lili Qian & Shengwang Jiang & Gaojun Xiao & Biao Li & Xiang Li & Wentao Cui, 2020. "Frameshift mutation in myostatin gene by zinc-finger nucleases results in a significant increase in muscle mass in Meishan sows," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 65(5), pages 182-191.

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