Muscle weakness in a mouse model of nemaline myopathy can be reversed with exercise and reveals a novel myofiber repair mechanism

Josephine E. Joya, Anthony J. Kee, Visalini Nair-Shalliker, Majid Ghoddusi, Mai Anh T Nguyen, Pradeep Luther, Edna C. Hardeman*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Patients with the inherited muscle disease nemaline myopathy experience prolonged muscle weakness following periods of immobility. We have examined endurance exercise as a means of improving recovery following muscle inactivity in our α-tropomyosinslow (Met9Arg)-transgenic mouse model of nemaline myopathy. Physical inactivity, mimicked using a hindlimb immobilization protocol, resulted in fiber atrophy and severe muscle weakness. Following immobilization, the nemaline mice (NM) were weaker than WT mice but regained whole-body strength with exercise training. The disuse-induced weakness and the regain of strength with exercise in NM were associated with the respective formation and resolution of nemaline rods, suggesting a role for rods in muscle weakness. Muscles from NM did not show the typical features of muscle repair during chronic stretch-immobilization of the soleus muscle (regeneration occurred with relative lack of centralized nuclei). This indicates that the normal process of regeneration may be altered in nemaline myopathy and may contribute to poor recovery. In conclusion, endurance exercise can alleviate disuse-induced weakness in NM. The altered myofiber repair process in the nemaline mice may be a response to primary myofibrillar damage that occurs in nemaline myopathy and is distinct from the classical repair in muscular dystrophy resulting from plasma membrane defects.

Original languageEnglish
Pages (from-to)2633-2645
Number of pages13
JournalHuman Molecular Genetics
Volume13
Issue number21
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

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    Joya, J. E., Kee, A. J., Nair-Shalliker, V., Ghoddusi, M., Nguyen, M. A. T., Luther, P., & Hardeman, E. C. (2004). Muscle weakness in a mouse model of nemaline myopathy can be reversed with exercise and reveals a novel myofiber repair mechanism. Human Molecular Genetics, 13(21), 2633-2645. https://doi.org/10.1093/hmg/ddh285