Myelinated axons fail to develop properly in a genetically authentic mouse model of Charcot-Marie-Tooth disease type 2E.

Myelinated axons fail to develop properly in a genetically authentic mouse model of Charcot-Marie-Tooth disease type 2E. Exp Neurol. 2018 Jun 22;: Authors: Lancaster E, Li J, Hanania T, Liem R, Scheideler MA, Scherer SS Abstract We have analyzed a mouse model of Charcot-Marie-Tooth disease 2E (CMT2E) harboring a heterozygous p.Asn98Ser (p.N98S) Nefl mutation, whose human counterpart results in a severe, early-onset neuropathy. Behavioral, electrophysiological, and pathological analyses were done on separate cohorts of NeflN98S/+ mutant mice and their wild type Nefl+/+ littermates between 8 and 48 weeks of age. The motor performance of NeflN98S/+ mice, as evidenced by altered balance and gait measures, was impaired at every age examined (from 6 to 25 weeks of age). At all times examined, myelinated axons were smaller and contained markedly fewer neurofilaments in NeflN98S/+ mice, in all examined aspects of the PNS, from the nerve roots to the distal ends of the sciatic and caudal nerves. Similarly, the myelinated axons in the various tracts of the spinal cord and in the optic nerves were smaller and contained fewer neurofilaments in mutant mice. The myelinated axons in both the PNS and the CNS of mutant mice had relatively thicker myelin sheaths. The amplitude and the nerve conduction velocity of the caudal nerves were reduced in proportion with the diminished sizes of myelinated axons. Conspicuous aggregations of neurofilaments w...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research