Expressing hNF-LE397K results in abnormal gaiting in a transgenic model of CMT2E.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gaiting, exacerbation of neuropathy, sensory defects and deafness. We generated a novel line of CMT2E mice expressing an hNF-L^E397K transgene, 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 showed that hNF-L^E397K mice developed abnormal gait of the hind limbs. The identification of severe gaiting defects in combination with previously observed muscle atrophy, reduced axon caliber and decreased nerve conduction velocity suggests that hNF-L^E397K mice recapitulate many of clinical signs associated with CMT2E. Therefore, hNF-L^E397K mice provide a context for potential therapeutic intervention. [ABSTRACT FROM AUTHOR]