Mdx5cv mice manifest more severe muscle dysfunction and diaphragm force deficits than do mdx mice

Nicholas Beastrom, Haiyan Lu, Allison MacKe, Benjamin D. Canan, Eric K. Johnson, Christopher M. Penton, Brian K. Kaspar, Louise R. Rodino-Klapac, Lan Zhou, Paul M.L. Janssen, Federica Montanaro

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle dysfunction leading to premature death by the third decade of life. The mdx mouse, the most widely used animal model of DMD, has been extremely useful to study disease mechanisms and to screen new therapeutics. However, unlike patients with DMD, mdx mice have a very mild motor function deficit, posing significant limitations for its use as a platform to assess the impact of treatments on motor function. It has been suggested that an mdx variant, the mdx5cv mouse, might be more severely affected. Here, we compared the motor activity, histopathology, and individual muscle force measurements of mdx and mdx5cv mice. Our study revealed that mdx5cv mice showed more severe exercise-induced fatigue, Rotarod performance deficits, and gait anomalies than mdx mice and that these deficits began at a younger age. Muscle force studies showed more severe strength deficits in the diaphragm of mdx5cv mice compared to mdx mice, but similar force generation in the extensor digitorum longus. Muscle histology was similar between the two strains. Differences in genetic background (genetic modifiers) probably account for these functional differences between mdx strains. Overall, our findings indicate that the mdx and mdx5cv mouse models of DMD are not interchangeable and identify the mdx5cv mouse as a valuable platform for preclinical studies that require assessment of muscle function in live animals.

Original languageEnglish (US)
Pages (from-to)2464-2474
Number of pages11
JournalAmerican Journal of Pathology
Volume179
Issue number5
DOIs
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Mdx<sup>5cv</sup> mice manifest more severe muscle dysfunction and diaphragm force deficits than do mdx mice'. Together they form a unique fingerprint.

  • Cite this

    Beastrom, N., Lu, H., MacKe, A., Canan, B. D., Johnson, E. K., Penton, C. M., Kaspar, B. K., Rodino-Klapac, L. R., Zhou, L., Janssen, P. M. L., & Montanaro, F. (2011). Mdx5cv mice manifest more severe muscle dysfunction and diaphragm force deficits than do mdx mice. American Journal of Pathology, 179(5), 2464-2474. https://doi.org/10.1016/j.ajpath.2011.07.009