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Muscle Nerve. 2012 Oct;46(4):588-91. doi: 10.1002/mus.23463.

Muscle function in a canine model of X-linked myotubular myopathy.

Author information

1
Department of Human Nutrition, Foods and Exercise, College of Agriculture & Life Sciences, Virginia Polytechnic and State University, Blacksburg, Virginia, USA 24060.

Abstract

INTRODUCTION:

We established a colony of dogs that harbor an X-linked MTM1 missense mutation.Muscle from affected male dogs exhibits reduction and altered localization of the MTM1 gene product, myotubularin, and provides a model analogous to X-linked myotubular myopathy (XLMTM).

METHODS:

We studied hindlimb muscle function in age-matched canine XLMTM genotypes between ages 9 and 18 weeks.

RESULTS:

By the end of the study, affected dogs produce only ∼15% of the torque generated by normals or carriers (0.023 ± 0.005 vs. 0.152 ± 0.007 and 0.154 ± 0.003 N-m/kg body mass, respectively, P < 0.05) and are too weak to stand unassisted. At this age, XLMTM dogs also demonstrate an abnormally low twitch:tetanus ratio, a right-shifted torque-frequency relationship and an increase in torque during repetitive stimulation (P < 0.05).

CONCLUSIONS:

We hypothesize that muscle weakness results from impaired excitation-contraction (E-C) coupling. Interventions that improve E-C coupling might be translated from the XLMTM dog model to patients.

PMID:
22987702
PMCID:
PMC3448125
DOI:
10.1002/mus.23463
[Indexed for MEDLINE]
Free PMC Article
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