Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

Abstract Charcot–Marie–Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L E397K , which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L E397K mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L E397K mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L E397K developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L E397K . Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L E397K mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L E397K mice provide a model for determining the efficacy of novel therapies.