PMID- 16041800
OWN - NLM
STAT- MEDLINE
DCOM- 20051130
LR  - 20061115
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 81
IP  - 6
DP  - 2005 Sep 15
TI  - Evidence for macrophage-mediated myelin disruption in an animal model for 
      Charcot-Marie-Tooth neuropathy type 1A.
PG  - 857-64
AB  - Charcot-Marie-Tooth neuropathy type 1A (CMT 1 A) is the most common inherited 
      neuropathy in humans and is mostly caused by a 1.5-Mb tandem duplication of 
      chromosome 17 comprising the gene for the peripheral myelin protein 22-kDa (PMP 
      22). Although there are numerous studies on the functional role of PMP 22, the 
      mechanisms of myelin degeneration under PMP 22-overexpression conditions have not 
      yet been fully understood. We have shown previously that in mouse mutants hetero- 
      or homozygously deficient for two other myelin components, P0 and C x 32, 
      respectively, immune cells contribute to the demyelinating neuropathy. To test 
      this possibility for PMP 22 overexpression, we investigated a putative mouse 
      model for CMT 1 A, i.e., the mouse strain C 6 1 mildly overexpressing human PMP 
      22 in peripheral nerves. Electron microscopic and electrophysiologic 
      investigations revealed that this mouse strain develops pathologic features 
      similar to those found in CMT 1 A patients. A novel finding, however, was the 
      upregulation of CD8- and F4/80-positive lymphocytes and macrophages, 
      respectively, in peripheral nerves. The observation that macrophages enter 
      endoneurial tubes of the mutants and obviously phagocytose morphologically normal 
      myelin strongly suggests that the myelin degeneration is mediated at least 
      partially by these phagocytic cells. By gene array technology and quantitative 
      RT-PCR of peripheral nerve homogenates from PMP 22 mutants, monocyte 
      chemoattractant protein-1 (MCP-1; cc l2) could be identified as a putative factor 
      to attract or activate macrophages that attack myelin sheaths in this model of 
      CMT 1 A.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Kobsar, Igor
AU  - Kobsar I
AD  - Developmental Neurobiology, Department of Neurology, University of Wurzburg, 
      Wurzburg, Germany.
FAU - Hasenpusch-Theil, Kerstin
AU  - Hasenpusch-Theil K
FAU - Wessig, Carsten
AU  - Wessig C
FAU - Muller, Hans Werner
AU  - Muller HW
FAU - Martini, Rudolf
AU  - Martini R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Myelin Proteins)
RN  - 0 (Pmp22 protein, mouse)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Axons/pathology
MH  - CD8-Positive T-Lymphocytes/immunology/physiology
MH  - Charcot-Marie-Tooth Disease/*pathology
MH  - Chemokine CCL2/biosynthesis
MH  - Demyelinating Diseases/pathology
MH  - Electrophysiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Immunoelectron
MH  - Myelin Proteins/genetics
MH  - Myelin Sheath/*pathology
MH  - Peripheral Nerves/metabolism/pathology
MH  - RNA/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sciatic Nerve/metabolism
MH  - Up-Regulation
EDAT- 2005/07/26 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/26 09:00
PHST- 2005/07/26 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/26 09:00 [entrez]
AID - 10.1002/jnr.20601 [doi]
PST - ppublish
SO  - J Neurosci Res. 2005 Sep 15;81(6):857-64. doi: 10.1002/jnr.20601.