(CMT1A) Depleting endogenous NT-3 enhances myelin formation in the Trembler-J mo

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J Neurosci Res. 2007 Jul 12

Depleting endogenous neurotrophin-3 enhances myelin formation in the

Trembler-J mouse, a model of a peripheral neuropathy.

Liu N, Varma S, Tsao D, Shooter EM, Tolwani RJ.

Department of Neurobiology, Stanford University School of Medicine,

Stanford, California.

The heterozygous Trembler-J (TrJ/+) mouse, containing a point

mutation in the peripheral myelin protein 22 (Pmp22) gene, is

characterized by severe hypomyelination and is a representative

model of Charcot-Marie-Tooth 1A (CMT1A) disease/Dejerine-Sottas

syndrome (DSS).

Given that the neurotrophin-3 (NT3)-TrkC signaling pathway is

inhibitory to myelination during development, we investigated the

role of the NT3-TrkC pathway in myelination and manipulated this

pathway to improve myelin formation in the CMT1A/DSS mouse model.

Injection of NT3 to the TrJ/+ mice decreased the myelin protein P(0)

level in the sciatic nerves. Suppressing the NT3-TrkC pathway with

TrkC-Fc, an NT3 scavenger, enhanced myelination in vitro and in vivo

in the TrJ/+ mouse.

Furthermore, we found that full-length TrkC was expressed in adult

TrJ/+ mouse sciatic nerves but was not detected in the wild-type

adults, suggesting that the full-length TrkC is a potential target

of treatment to enhance myelination in the TrJ/+ mouse.