Journal article
Conduction Block in PMP22 Deficiency
The Journal of neuroscience, Vol.30(2), pp.600-608
01/13/2010
DOI: 10.1523/JNEUROSCI.4264-09.2010
PMCID: PMC3676309
PMID: 20071523
Abstract
Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis, we induced 60–70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two
pmp22
alleles (
pmp22
+/−
). Induction time for the CB was significantly shorter in
pmp22
+/−
mice than that in
pmp22
+/+
mice. This shortened induction was also found in
myelin-associated glycoprotein
knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin.
Pmp22
+/−
nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [
3
H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.
Details
- Title: Subtitle
- Conduction Block in PMP22 Deficiency
- Creators
- Yunhong Bai - Department of Neurology, Wayne State University, andXuebao Zhang - Department of Neurology, Wayne State University, andIstvan Katona - Department of Neurology, Wayne State University, andMario Andre Saporta - Department of Neurology, Wayne State University, andMichael E Shy - Department of Neurology, Wayne State University, andHeather A O'Malley - Department of Pharmacology and Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, andLori L Isom - Department of Pharmacology and Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, andUeli Suter - Department of Biology, Institute of Cell Biology, Eidgenössische Technische Hochschule Zürich, 8093 Zurich, SwitzerlandJun Li - Department of Neurology, Wayne State University, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.30(2), pp.600-608
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.4264-09.2010
- PMID
- 20071523
- PMCID
- PMC3676309
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 01/13/2010
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020762602771
Metrics
11 Record Views