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.