APPS November 2002 Meeting Abstract 2404


Nicole Stupka, Paul Gregorevic, David R. Plant, Gordon S. Lynch, Muscle Mechanics Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.

Although the genotype of the mdx mouse is similar to that of boys with Duchenne muscular dystrophy, the mouse has a much more benign phenotype. Mdx mice undergo severe muscle degeneration at 3 to 4 weeks of age, but a high regenerative capacity ensures almost complete functional recovery of their limb skeletal muscles. The cellular mechanisms responsible for this enhanced regenerative capacity are not well understood. We tested the hypothesis that the calcineurin (CaN) signalling pathway is essential for muscle regeneration in young mdx mice and that inhibition of this pathway using cyclosporine A (CsA) would increase the severity of the dystrophic phenotype. Young (17 day old) mdx and C57BL/10 control mice received either CsA (30 mg/kg body mass, i.p. daily) or an equivalent volume of vehicle for 2 weeks. Following treatment, the absolute increase in body mass and the average increase in body mass per day was lower in the CsA treated mdx mice than in vehicle treated mdx mice or vehicle and CsA treated C57BL/10 mice. CsA administration decreased EDL, soleus, plantaris, and tibialis anterior muscle mass in mdx mice, but had no effect on muscle mass in C57BL/10 mice. CsA treatment increased the amount of visible connective tissue in the hindlimb muscle of mdx but not C57/BL10 mice. CsA administration decreased the maximum force of both the EDL and soleus muscles in mdx but not C57BL/10 mice when compared to their vehicle treated littermates. CsA administration did not increase the susceptibility to fatigue or the compromise the recovery of force in either mdx or C57BL/10 mice. We conclude that inhibition of the CaN pathway compromises the regenerative capacity of young mdx mice as evidenced by the decreased growth, muscle mass and function following CsA treatment, but it does not affect growth or muscle function of young C57BL/10 mice.

Supported by the Muscular Dystrophy Association (USA).

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