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Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice

Nature Medicine volume 3, pages 1216–1221 (1997)Cite this article

Abstract

Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trc-utrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.

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Author notes

  1. Nicolas Deconinck and Jonathon Tinsley: These authors contributed equally to this work.

Authors and Affiliations

  1. Département de Physiologie, UCL 5540, Université Catholique de Louvain, Avenue Hippocrate 55, 1200, Brussels, Belgium

    Nicolas Deconinck, Fabienne De Backer, David Kahn & Jean-Marie Gillis

  2. Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Jonathon Tinsley, Rosie Fisher, Steve Phelps & Kay Davies

Authors
  1. Nicolas Deconinck
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  2. Jonathon Tinsley
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  7. Kay Davies
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  8. Jean-Marie Gillis
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Correspondence to Jean-Marie Gillis.

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Deconinck, N., Tinsley, J., Backer, F. et al. Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice. Nat Med 3, 1216–1221 (1997). https://doi.org/10.1038/nm1197-1216

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