Locomotor and skeletal muscle abnormalities in trembler J neuropathic mice

Muscle Nerve. 2018 Apr;57(4):664-671. doi: 10.1002/mus.25987. Epub 2017 Oct 24.

Abstract

Introduction: Patients with hereditary peripheral neuropathies exhibit characteristic deformities of the hands and feet and have difficulty ambulating. To examine to what extent neuropathic animals recapitulate these deficits, we studied trembler J (TrJ) mice, which model early-onset demyelinating neuropathy.

Methods: A cohort of 4-month-old female wild type and neuropathic mice were evaluated for locomotor measurements, neuromuscular function, and skeletal muscle proteolysis and morphometry.

Results: Utilizing the DigiGait imaging system, we identified pronounced alterations in forepaw and hindpaw angles and a decrease in hindpaw area on the treadmill in neuropathic rodents. Torque production by the tibialis anterior (TA) muscle was significantly weakened and was paralleled by a decrease in myofiber cross-sectional area and an increase in muscle tissue proteolysis.

Discussion: Our findings in TrJ mice reflect the phenotypic presentation of the human neuropathy in which patients exhibit weakness of the TA muscle resulting in foot drop and locomotor abnormalities. Muscle Nerve 57: 664-671, 2018.

Keywords: Charcot-Marie-Tooth disease; demyelination; muscle atrophy; neuromuscular function; neuropathy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / physiopathology*
  • Disease Models, Animal
  • Female
  • Gait Analysis
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Hereditary Sensory and Motor Neuropathy / physiopathology
  • Locomotion / physiology*
  • Mice
  • Muscle, Skeletal / physiopathology*
  • Myelin Proteins / genetics
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / physiopathology
  • Phenotype
  • Torque

Substances

  • Myelin Proteins
  • Pmp22 protein, mouse