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The mdx mouse as a model for carnitine deficiency in the pathogenesis of duchenne muscular dystrophy
Author(s) -
Zolkipli Zarazuela,
Mai Lydia,
Lamhonwah AnneMarie,
Tein Ingrid
Publication year - 2012
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.23368
Subject(s) - carnitine , medicine , duchenne muscular dystrophy , endocrinology , mdx mouse , skeletal muscle , muscular dystrophy , ventricle , diaphragm (acoustics) , mitochondrial biogenesis , biology , chemistry , mitochondrion , dystrophin , biochemistry , physics , acoustics , loudspeaker
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‐DMD mdx /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