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Functional assessment of skeletal muscle in intact mice lacking myostatin by concurrent NMR imaging and spectroscopy

Gene Therapy volume 17, pages 328–337 (2010)Cite this article

Abstract

Inhibiting myostatin (mstn) causes spectacular increase in muscle mass, spurring research for therapeutic approaches against neuromuscular disorders. Yet, possible functional deterioration and compromised force production have been reported in isolated muscle of null mstn(−/−) mice. We analyzed vascular and metabolic response to repeated electro-stimulated exercise in vivo in mstn−/− mice compared with FVB wild-type controls (WT), using interleaved multi-parametric functional nuclear magnetic resonance (NMR) imaging and spectroscopy. At steady-state exercise, specific force of plantar flexion, phosphocreatine consumption measured by phosphorus spectroscopy and maximum perfusion measured by arterial spin-labeled (ASL) NMR imaging were identical in both groups. After exercise, phosphorus spectroscopy revealed reduced oxidative mitochondrial capacity in mstn−/−, whereas early recovery perfusion was identical and oxygen extraction, estimated from the blood oxygen level-dependent (BOLD) contrast, was decreased when compared with WT. Hyperemia was prolonged, indicating specific regulation of the perfusional response in mstn−/− mice. Histology showed an increased proportion of type IIb fibers in hypertrophied muscles, but the distribution of capillary contacts per fiber between oxidative and glycolytic fibers was unaltered in mstn−/− compared with WT. These integrated results formed coherent evidence of a congruous, non-pathologic shift toward a more glycolytic metabolism in this model of mstn−/−.

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Acknowledgements

We thank Dr Jean-Yves Hogrel (Institute of Myology, Paris) for helpful discussion on force measurements, Dr Vincent Molinié (Anatomopathology Department, GH St Joseph, Paris) for immunostaining and Aurélien Monnet for technical assistance.

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Authors and Affiliations

  1. Institute of Myology, NMR Laboratory, Paris, France

    C Baligand, J C Ménard, C Wary & P G Carlier

  2. CEA, I2BM, MIRCen, IdM NMR Laboratory, Paris, France

    C Baligand, J C Ménard, C Wary & P G Carlier

  3. UPMC Univ Paris 06, Paris, France,

    C Baligand, J C Ménard, C Wary & P G Carlier

  4. Unité de diabétologie et de nutrition, Université Catholique de Louvain, Brussels, Belgium

    H Gilson, O Schakman & J-P Thissen

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  1. C Baligand
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Correspondence to P G Carlier.

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Baligand, C., Gilson, H., Ménard, J. et al. Functional assessment of skeletal muscle in intact mice lacking myostatin by concurrent NMR imaging and spectroscopy. Gene Ther 17, 328–337 (2010). https://doi.org/10.1038/gt.2009.141

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  • DOI: https://doi.org/10.1038/gt.2009.141

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