Muscle pathology without severe nerve pathology in a new mouse model of Charcot-Marie-Tooth disease type 2E.

ABSTRACT: Mutations in neurofilament light (NF-L) have been linked to Charcot-Marie-Tooth disease type 2E (CMT2E) in humans. To provide insight into disease pathogenesis, we developed a novel line of CMT2E mice that constitutively express human NF-L (hNF-L) with a glutamic acid to lysine mutation at position 397 (hNF-L(E397K)). This new line of mice developed signs consistent with CMT2E patients. Disease signs were first observed at 4 months in hNF-L(E397K) mice, and consisted of aberrant hind limb posture, digit deformities, reduced voluntary locomotor activity, reduced motor nerve conduction velocities (MNCVs) and muscle atrophy. Reduced voluntary locomotor activity and muscle pathology occurred without significant denervation, and hNF-L(E397K) mice showed relatively mild signs of nerve pathology.

SUBMITTER: Shen H 

PROVIDER: S-EPMC3109999 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature