The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice

Stupka, Nicole, Gregorevic, Paul, Plant, David R. and Lynch, Gordon S. 2004, The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice, Acta Neuropathologica, vol. 107, no. 4, pp. 299-310.

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Title The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice
Formatted title The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice
Author(s) Stupka, Nicole
Gregorevic, Paul
Plant, David R.
Lynch, Gordon S.
Journal name Acta Neuropathologica
Volume number 107
Issue number 4
Start page 299
End page 310
Publisher Springer Berlin / Heidelberg
Place of publication Berlin, Germany
Publication date 2004-04
ISSN 0001-6322
1432-0533
Keyword(s) skeletal muscle
duchenne muscular dystrophy
calcineurin
regeneration
cyclosporine A
Summary Although mdx mice share the same genetic defect and lack dystrophin expression as in Duchenne muscular dystrophy (DMD), their limb muscles have a high regenerative capacity that ensures a more benign phenotype and essentially normal function. The cellular pathways responsible for this enhanced regenerative capacity are unknown. We tested the hypothesis that the calcineurin signal transduction pathway is essential for the successful regeneration following severe degeneration observed in the limb muscles of young mdx mice (2–4 weeks old) and that inhibition of this pathway using cyclosporine A (CsA) would exacerbate the dystrophic pathology. Eighteen-day-old mdx and C57BL/10 mice were treated with CsA for 16 days. CsA administration severely disrupted muscle regeneration in mdx mice, but had minimal effect in C57BL/10 mice. Muscles from CsA-treated mdx mice had fewer centrally nucleated fibers and extensive collagen, connective tissue, and mononuclear cell infiltration than muscles from vehicle-treated littermates. The deleterious effects of CsA on muscle morphology were accompanied by a 30–35% decrease in maximal force producing capacity. Taken together, these observations indicate that the calcineurin signal transduction pathway is a significant determinant of successful skeletal muscle regeneration in young mdx mice. Up-regulating this pathway may have clinical significance for DMD.
Language eng
Field of Research 060110 Receptors and Membrane Biology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, Springer-Verlag
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019981

Document type: Journal Article
Collection: Institute for Technology Research and Innovation
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Created: Mon, 28 Sep 2009, 17:49:25 EST by Nicole Stupka

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