PMID- 9469571
OWN - NLM
STAT- MEDLINE
DCOM- 19980330
LR  - 20231213
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 51
IP  - 2
DP  - 1998 Jan 15
TI  - Abnormalities in the axonal cytoskeleton induced by a connexin32 mutation in 
      nerve xenografts.
PG  - 174-84
AB  - The X-linked form of Charcot-Marie-Tooth neuropathy is associated with mutations 
      in the connexin32 (Cx32) gene. The functional role of Cx32 in Schwann cells and 
      the relationship of these mutations to the progressive axonal loss and distal 
      limb weakness seen in this disease have not been elucidated. To investigate the 
      local influence of Schwann cells bearing the Cx32 gene defect on axonal 
      cytoskeleton and the myelination process, the nerve xenograft model was used to 
      transfer a Cx32 missense mutation (Glu102Gly) from human to an in vivo 
      myelination system in nude mice. Twelve nerve grafts from two family members with 
      Cx32 mutations and 17 grafts from three healthy individuals were generated by 
      end-to-end anastomosis of approximately 6-mm sural nerve fascicles into the cut 
      ends of the sciatic nerve in nude mice. Specimens were examined at 2, 4, 8, 12, 
      and 16 weeks. Ultrastructural morphometric analysis showed Schwann cells with 
      Cx32 mutation have a profound effect on the nude mice axons, resulting in an 
      increase in neurofilament density, a depletion of microtubules associated with 
      fragmentation of smooth axonal reticulum, and increased vesicles and 
      mitochondria. At 16 weeks, axonal enlargement was evident within the proximal 
      part of the graft; axonal atrophy, degeneration, and fiber loss were seen in 
      distal-graft and host segments. The myelination process was not affected. We 
      conclude that Cx32 mutation impairs a modulatory function of Schwann cells on 
      axons, resulting in profound cytoskeletal alterations leading to distal axonal 
      degeneration. These observations emphasize the role of impaired Schwann cell-axon 
      interactions in the pathogenesis of hereditary neuropathies.
FAU - Sahenk, Z
AU  - Sahenk Z
AD  - Department of Neurology, Neuromuscular Disease Center, The Ohio State University, 
      Columbus 43210, USA. Sahenk.1@osu.edu
FAU - Chen, L
AU  - Chen L
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 (Connexins)
SB  - IM
EIN - J Neurosci Res 1999 Jan 15;55(2):268
MH  - Animals
MH  - Axons/*physiology/ultrastructure
MH  - Brain Tissue Transplantation/*physiology
MH  - Charcot-Marie-Tooth Disease/genetics/pathology
MH  - Connexins/*genetics
MH  - Cytoskeleton/*physiology/ultrastructure
MH  - Endoplasmic Reticulum, Smooth/physiology/ultrastructure
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Microtubules/physiology/ultrastructure
MH  - Mutation/*physiology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Schwann Cells/physiology/ultrastructure
MH  - Transplantation, Heterologous/*physiology
MH  - Gap Junction beta-1 Protein
EDAT- 1998/02/20 03:03
MHDA- 2000/06/20 09:00
CRDT- 1998/02/20 03:03
PHST- 1998/02/20 03:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/02/20 03:03 [entrez]
AID - 10.1002/(SICI)1097-4547(19980115)51:2<174::AID-JNR6>3.0.CO;2-A [pii]
AID - 10.1002/(SICI)1097-4547(19980115)51:2<174::AID-JNR6>3.0.CO;2-A [doi]
PST - ppublish
SO  - J Neurosci Res. 1998 Jan 15;51(2):174-84. doi: 
      10.1002/(SICI)1097-4547(19980115)51:2<174::AID-JNR6>3.0.CO;2-A.