This article is published as part of the AFM BioMed Conference on Life Sciences and Medicine, Paris 2011 of the Journal of Molecular Recognition, edited by Simon Scheuring, Pierre Parot and Jean-Luc Pellequer.
Myelinating and demyelinating phenotype of Trembler-J mouse (a model of Charcot–Marie–Tooth human disease) analyzed by atomic force microscopy and confocal microscopy†
Article first published online: 19 APR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Molecular Recognition
Special Issue: AFM BioMed Conference on Life Sciences and Medicine, Paris 2011
Volume 25, Issue 5, pages 247–255, May 2012
How to Cite
Rosso, G., Negreira, C., Sotelo, J. R. and Kun, A. (2012), Myelinating and demyelinating phenotype of Trembler-J mouse (a model of Charcot–Marie–Tooth human disease) analyzed by atomic force microscopy and confocal microscopy. J. Mol. Recognit., 25: 247–255. doi: 10.1002/jmr.2176
- Issue published online: 19 APR 2012
- Article first published online: 19 APR 2012
- Manuscript Received: 31 OCT 2011
- Manuscript Accepted: 27 JAN 2011
- Manuscript Revised: 13 JAN 2011
- atomic force microscopy;
- nerve topography;
- mechanical properties;
- Trembler-J mouse;
The accumulation of misfolded proteins is associated with various neurodegenerative conditions. Mutations in PMP-22 are associated with the human peripheral neuropathy, Charcot–Marie–Tooth Type 1A (CMT1A). PMP-22 is a short-lived 22 kDa glycoprotein, which plays a key role in the maintenance of myelin structure and compaction, highly expressed by Schwann cells. It forms aggregates when the proteasome is inhibited or the protein is mutated. This study reports the application of atomic force microscopy (AFM) as a detector of profound topographical and mechanical changes in Trembler-J mouse (CMT1A animal model). AFM images showed topographical differences in the extracellular matrix and basal lamina organization of Tr-J/+ nerve fibers. The immunocytochemical analysis indicated that PMP-22 protein is associated with type IV collagen (a basal lamina ubiquitous component) in the Tr-J/+ Schwann cell perinuclear region. Changes in mechanical properties of single myelinating Tr-J/+ nerve fibers were investigated, and alterations in cellular stiffness were found. These results might be associated with F-actin cytoskeleton organization in Tr-J/+ nerve fibers. AFM nanoscale imaging focused on topography and mechanical properties of peripheral nerve fibers might provide new insights into the study of peripheral nervous system diseases. Copyright © 2012 John Wiley & Sons, Ltd.