Cancer Institute A national cancer institute
designated cancer center

Joseph Shrager

Publication Details

  • Inspiratory loading does not accelerate dystrophy in mdx mouse diaphragm: implications for regenerative therapy JOURNAL OF APPLIED PHYSIOLOGY Krupnick, A. S., Zhu, J. L., Nguyen, T., Kreisel, D., Balsara, K. R., Lankford, E. B., Clark, C. C., LEVINE, S., Stedman, H. H., Shrager, J. B. 2003; 94 (2): 411-419

    Abstract:

    Since the finding that the mdx mouse diaphragm, in contrast to limb muscles, undergoes progressive degeneration analogous to that seen in Duchenne muscular dystrophy, the relationship between the workload on a muscle and the pathogenesis of dystrophy has remained controversial. We increased the work performed by the mdx mouse diaphragm in vivo by tracheal banding and evaluated the progression of dystrophic changes in that muscle. Despite the establishment of dramatically increased respiratory workload and accelerated myofiber damage documented by Evans blue dye, no change in the pace of progression of dystrophy was seen in banded animals vs. unbanded, sham-operated controls. At the completion of the study, more centrally nucleated fibers were evident in the diaphragms of banded mdx mice than in sham-operated mdx controls, indicating that myofiber regeneration increases to meet the demands of the work-induced damage. These data suggest that there is untapped regenerative capacity in dystrophin-deficient muscle and validates experimental efforts aimed at augmenting regeneration within skeletal muscle as a therapeutic strategy in the treatment of dystrophinopathies.

    View details for DOI 10.1152/japplphysiol.00689.2002

    View details for Web of Science ID 000180437600001

    View details for PubMedID 12531909

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