Animal models of inherited neuropathies.

Mutations in a number of genes have been associated with inherited neuropathies (Charcot-Marie-Tooth or CMT disease). This review highlights how animal models of demyelinating CMT have improved our understanding of disease mechanisms. Transgenic CMT models also allow therapies to be developed in a preclinical setting.,Rodent models for the most common subtypes of human CMT disease are now available, and two mouse mutants modeling the rare CMT4B subform have lately extended this repertoire. In a peripheral myelin protein 22 kDa (Pmp22) transgenic rat model of CMT1A, administration of a progesterone receptor antagonist reduced Pmp22 overexpression, axon loss and clinical impairments. Dietary ascorbic acid prevented dysmyelination and premature death in a Pmp22 transgenic mouse line. Neurotrophin-3 promoted small fiber remyelination in CMT1A xenografts and sensory functions in CMT1A patients. Gene expression profiling in rodent models of CMT may identify further therapeutical targets. While original classifications distinguish the demyelinating and axonal forms of CMT, recent findings emphasize that axon loss is a common feature, possibly caused by Schwann cell defects rather than demyelination per se. This supports our model that myelination and long-term axonal support are distinct functions of all myelinating glial cells.,Animal models have opened up new perspectives on the pathomechanisms and possible treatment strategies of inherited neuropathies.