title: Muscle function in a canine model of X-linked myotubular myopathy.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Human Nutrition, Foods and Exercise, College of Agriculture & Life Sciences, Virginia Polytechnic and State University, Blacksburg, Virginia, USA 24060.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grange
authors.forename: Jon
authors.initials: J
authors.lastname: Doering
authors.forename: Erin
authors.initials: E
authors.lastname: Mitchell
authors.forename: Melanie N
authors.initials: MN
authors.lastname: Holder
authors.forename: Xuan
authors.initials: X
authors.lastname: Guan
authors.forename: Melissa
authors.initials: M
authors.lastname: Goddard
authors.forename: Christopher
authors.initials: C
authors.lastname: Tegeler
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
authors.forename: Martin K
authors.initials: MK
authors.lastname: Childers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020125:Mutation, Missense; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000503:physiopathology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin