Document Detail


Distal axonopathy in peripheral nerves of PMP22-mutant mice.
MedLine Citation:
PMID:  10430839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A partial duplication of chromosome 17 is associated with Charcot-Marie-Tooth disease type 1A (CMT1A), a demyelinating peripheral neuropathy that causes progressive distal muscle atrophy and sensory impairment. Trisomic expression of peripheral myelin protein 22 (PMP22) whose gene is contained within the duplicated region is considered to be responsible for the disease. By using recombinant gene technology in rodents, we had demonstrated previously that PMP22 is sensitive to gene dosage. Homozygous PMP22 knockout (PMP22(0/0)) mice and transgenic animals carrying additional copies of the PMP22 gene develop distinct peripheral polyneuropathies. We have now performed a detailed morphometrical analysis of the L3 roots, quadriceps and saphenous nerves of these PMP22-mutant mice to study whether the myelin and potential axonal deficits are evenly distributed. The L3 roots and the peripheral nerves were chosen as representatives of the proximal and distal segments of the peripheral nervous system. When the roots were compared with the peripheral nerves, myelin deficiencies appeared more severe at the radicular levels, in particular the ventral roots. Decreased numbers of large calibre axons were a prominent feature in the motor branches of both strains of PMP22-mutant mice, and these axonal deficits were more severe distally. Active axonal damage was only observed in the nerves of PMP22(0/0) mice. Despite the distinct effects on myelination and the Schwann cell phenotype that characterize the neuropathies of PMP22-mutant mice, both strains develop a distally accentuated axonopathy as a common disease mechanism which is likely to be responsible for the neurological deficits.
Authors:
S Sancho; J P Magyar; A Aguzzi; U Suter1
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  122 ( Pt 8)     ISSN:  0006-8950     ISO Abbreviation:  Brain     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-09-07     Completed Date:  1999-09-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1563-77     Citation Subset:  AIM; IM    
Affiliation:
Department of Cell Biology, Swiss Federal Institute of Technology and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / pathology*
Gene Dosage
Heterozygote
Homozygote
Humans
Mice
Mice, Knockout
Mice, Transgenic
Muscle, Skeletal / innervation
Myelin Proteins / deficiency,  genetics*,  physiology*
Nerve Fibers, Myelinated / pathology*
Peripheral Nerves / pathology*
Peripheral Nervous System Diseases / genetics,  pathology
Schwann Cells / pathology
Chemical
Reg. No./Substance:
0/Myelin Proteins; 0/PMP22 protein, human; 0/Pmp22 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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