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

Muscle Nerve. 2012 Nov;46(5):767-72. doi: 10.1002/mus.23368.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnitine / deficiency*
  • Carnitine / genetics
  • Disease Models, Animal*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscular Dystrophy, Duchenne / etiology
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism*
  • Quadriceps Muscle / physiopathology
  • Vitamin B Deficiency / complications
  • Vitamin B Deficiency / genetics*
  • Vitamin B Deficiency / metabolism*

Substances

  • Carnitine