Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy

✍ Scribed by Ning Liu; Sushama Varma; David Tsao; Eric M. Shooter; Ravi J. Tolwani

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 258 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21388

✦ Synopsis

Abstract

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. © 2007 Wiley‐Liss, Inc.