ALTERED NEUROFILAMENT PHOSPHORYLATION AND BETA-TUBULIN ISOTYPES IN CHARCOT-MARIE-TOOTH DISEASE TYPE-1

Charcot-Marie-Tooth disease type 1 (CMT1) is associated with atrophy a nd degeneration of peripheral nerve axons in addition to prominent cha nges in the structure of Schwann cells. We have investigated the compo sition of the axonal cytoskeleton in sural nerve biopsies from patient s with CMT1. Compared to controls, CMT1 nerves exhibited marked hypoph osphorylation of neurofilament proteins and an increased relative abun dance of beta tubulin isotypes 2 and 3. Biopsies from patients with ot her causes of neuropathy, matched to the CMT1 group for severity of ax onal atrophy, exhibited an intermediate degree of neurofilament hypoph osphorylation and no abnormality of tubulin isotypes. The axonal cytos keleton in CMT1 resembles that of immature nerve fibers. A failure of normal Schwann cell-axon interaction in CMT1 may prevent full differen tiation of the axonal cytoskeleton of myelinated nerve fibers.