Enhancement of Schwann cell myelin formation by K252a in the Trembler-J mouse
dorsal root ganglion explant culture.
Liu N, Varma S, Shooter EM, Tolwani RJ.
Department of Neurobiology, School of Medicine Stanford University, 299 Campus
Drive, Fairchild Building D225, Stanford, CA 94305, USA. nliu@cmgm.stanford.edu
The Trembler-J (TrJ) mouse, containing a point mutation in the peripheral myelin
protein 22 gene, is characterized by severe hypomyelination and is a
representative model of Charcot-Marie-Tooth 1A disease/Dejerine-Sottas Syndrome.
Previous studies have shown that protein kinase inhibitor K252a enhances
wild-type Schwann cell myelination in culture. We used a dorsal root ganglion (DRG)
explant culture system from the heterozygous TrJ/+ mouse to investigate if
myelination could be enhanced by K252a. The TrJ/+ DRG explant cultures
replicated some important features of the TrJ/+ mouse, showing reduced myelin
protein accumulation, thinner myelin sheaths, and shortened myelin internodes.
K252a increased myelin protein accumulation and myelin sheath thickness but did
not substantially increase myelin internode length. Furthermore, the TrJ/+ DRG
explant culture and sciatic nerves continued to respond to K252a during the
stage when myelination is complete in the wild type. A general tyrosine kinase
inhibitor, genistein, but not inhibitors of serine/threonine protein kinase
inhibitors, had a similar effect to K252a. K252a is therefore able to partially
overcome hypomyelination by enhancing mutant Schwann cell myelin formation in
the TrJ/+ mouse.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Cheap Reseller Hosting 
