Document Detail

Distal axonopathy in peripheral nerves of PMP22-mutant mice.
MedLine Citation:
PMID:  10430839     Owner:  NLM     Status:  MEDLINE    
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.
S Sancho; J P Magyar; A Aguzzi; U Suter1
Related Documents :
6112019 - Net sulfatide synthesis, galactosylceramide sulfotransferase and arylsulfatase a activi...
11512669 - Leukocyte recruitment and neuroglial activation during facial nerve regeneration in ica...
19497309 - Protective effects of progesterone administration on axonal pathology in mice with expe...
1378089 - Tumour necrosis factor causes an increase in axonal transport of protein and demyelinat...
20544279 - Beneficial effects of minocycline on cuprizone induced cortical demyelination.
18486939 - Role of b:t cell ratio in suppression of clinical signs: a model for silent ms.
22244329 - Hydrogen sulfide-linked sulfhydration of nf-κb mediates its antiapoptotic actions.
15285999 - C-type natriuretic peptide attenuates bleomycin-induced pulmonary fibrosis in mice.
1690299 - Interferon activity is not detected in blastocyst secretions and does not induce decidu...
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    
Department of Cell Biology, Swiss Federal Institute of Technology and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Axons / pathology*
Gene Dosage
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
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

Previous Document:  A cerebellar-like terminal and postural tremor induced in normal man by transcranial magnetic stimul...
Next Document:  Differential expression of matrix metalloproteinases in bacterial meningitis.