The mdx mouse as a model for carnitine deficiency in the pathogenesis of duchenne muscular dystrophy

Authors

  • Zarazuela Zolkipli MBChB,

    1. Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Lydia Mai MSc,

    1. Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Anne-Marie Lamhonwah PhD,

    1. Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Ingrid Tein MD

    Corresponding author
    1. Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    • Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
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Abstract

Introduction: Muscle and cardiac metabolism are dependent on the oxidation of fats and glucose for adenosine triphosphate production, for which L-carnitine is an essential cofactor. Methods: We measured muscle carnitine concentrations in skeletal muscles, diaphragm, and ventricles of C57BL/10ScSn-DMDmdx/J mice (n = 10) and compared them with wild-type C57BL/6J (n = 3), C57BL/10 (n = 10), and C3H (n = 12) mice. Citrate synthase (CS) activity was measured in quadriceps/gluteals and ventricles of mdx and wild-type mice. Results: We found significantly lower tissue carnitine in quadriceps/gluteus (P < 0.05) and ventricle (P < 0.05), but not diaphragm of mdx mice, when compared with controls. CS activity was increased in mdx quadriceps/gluteus (P < 0.03) and ventricle (P < 0.02). This suggests compensatory mitochondrial biogenesis. Conclusions: Decreased tissue carnitine has implications for reduced fatty acid and glucose oxidation in mdx quadriceps/gluteus and ventricle. The mdx mouse may be a useful model for studying the role of muscle carnitine deficiency in DMD bioenergetic insufficiency and providing a targeted and timed rationale for L-carnitine therapy. Muscle Nerve 46: 767–772, 2012

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