A report of this study was presented at the 2005 meeting of the Society for Neuroscience.
Subtle myelin defects in PLP-null mice †
Version of Record online: 26 JUN 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 54, Issue 3, pages 172–182, 15 August 2006
How to Cite
Rosenbluth, J., Nave, K.-A., Mierzwa, A. and Schiff, R. (2006), Subtle myelin defects in PLP-null mice . Glia, 54: 172–182. doi: 10.1002/glia.20370
- Issue online: 12 JUL 2006
- Version of Record online: 26 JUN 2006
- Manuscript Accepted: 11 MAY 2006
- Manuscript Received: 9 JAN 2006
- NIH. Grant Number: NS 37475
- National MS Society. Grant Number: RG 2539
- multiple sclerosis;
This study explores subtle defects in the myelin of proteolipid protein (PLP)-null mice that could potentially underlie the functional losses and axon damage known to occur in this mutant and in myelin diseases including multiple sclerosis. We have compared PLP-null central nervous system (CNS) myelin with normal myelin using ultrastructural methods designed to emphasize fine differences. In the PLP-null CNS, axons large enough to be myelinated often lack myelin entirely or are surrounded by abnormally thin sheaths. Short stretches of cytoplasm persist in many myelin lamellae. Most strikingly, compaction is incomplete in this mutant as shown by the widespread presence of patent interlamellar spaces of variable width that can be labeled with ferricyanide, acting as an aqueous extracellular tracer. In thinly myelinated fibers, interlamellar spaces are filled across the full width of the sheaths. In thick myelin sheaths, they appear filled irregularly but diffusely. These patent spaces constitute a spiral pathway through which ions and other extracellular agents may penetrate gradually, possibly contributing to the axon damage known to occur in this mutant, especially in thinly myelinated fibers, where the spiral path length is shortest and most consistently labeled. We show also that the “radial component” of myelin is distorted in the mutant (“diagonal component”), extending across the sheaths at 45° instead of 90°. These observations indicate a direct or indirect role for PLP in maintaining myelin compaction along the external surfaces of the lamellae and to a limited extent, along the cytoplasmic surfaces as well and also in maintaining the normal alignment of the radial component. © 2006 Wiley-Liss, Inc.