Locomotor and Skeletal Muscle Abnormalities in Trembler J Neuropathic Mice

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 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 fore- and hindpaw angles and a decrease in hindpaw area on the treadmill in neuropathic rodents. Muscle torque production by the tibialis anterior was significantly weakened, and was paralleled by a decrease in myofiber cross-sectional area and muscle tissue proteolysis. Discussion: Our findings in Trembler J mice reflect the phenotypic presentation of the human neuropathy where patients exhibit weakness of the tibialis anterior muscle resulting in foot drop and locomotor abnormalities. This article is protected by copyright. All rights reserved.