PMID- 15703409
OWN - NLM
STAT- MEDLINE
DCOM- 20050926
LR  - 20231213
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 25
IP  - 6
DP  - 2005 Feb 9
TI  - Transgenic expression of human connexin32 in myelinating Schwann cells prevents 
      demyelination in connexin32-null mice.
PG  - 1550-9
AB  - Mutations in Gap Junction beta1 (GJB1), the gene encoding the gap junction 
      protein connexin32 (Cx32), cause the X-linked form of Charcot-Marie-Tooth disease 
      (CMT1X), an inherited demyelinating neuropathy. We investigated the possibility 
      that the expression of mutant Cx32 in other cells besides myelinating Schwann 
      cells contributes to the development of demyelination. Human Cx32 was expressed 
      in transgenic mice using a rat myelin protein zero (Mpz) promoter, which is 
      exclusively expressed by myelinating Schwann cells. Male mice expressing the 
      human transgene were crossed with female Gjb1/cx32-null mice; the resulting male 
      offspring were all cx32-null (on the X chromosome), and one-half were transgene 
      positive. In these transgenic mice, all of the Cx32 was derived from the 
      expression of the transgene and was found in the sciatic nerve but not in the 
      spinal cord or the liver. Furthermore, the Cx32 protein was properly localized 
      (within incisures and paranodes) in myelinating Schwann cells. Finally, the 
      expression of human Cx32 protein "rescued" the phenotype of cx32-null mice, 
      because the transgenic mice have significantly fewer demyelinated or remyelinated 
      axons than their nontransgenic littermates. These results indicate that the loss 
      of Schwann-cell-autonomous expression of Cx32 is sufficient to account for 
      demyelination in CMT1X.
FAU - Scherer, Steven S
AU  - Scherer SS
AD  - Department of Neurology and Cell and Molecular Biology Graduate Group, The 
      University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6077, 
      USA.
FAU - Xu, Yi-Tian
AU  - Xu YT
FAU - Messing, Albee
AU  - Messing A
FAU - Willecke, Klaus
AU  - Willecke K
FAU - Fischbeck, Kenneth H
AU  - Fischbeck KH
FAU - Jeng, Linda Jo Bone
AU  - Jeng LJ
LA  - eng
GR  - R01 NS042878/NS/NINDS NIH HHS/United States
GR  - R01 NS08075/NS/NINDS NIH HHS/United States
GR  - R01 NS42878/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Connexins)
RN  - 0 (Myelin P0 Protein)
SB  - IM
MH  - Animals
MH  - Axons/physiology
MH  - Cell Count
MH  - Charcot-Marie-Tooth Disease/genetics/*metabolism/pathology
MH  - Connexins/biosynthesis/genetics/*physiology
MH  - Female
MH  - Femoral Nerve/pathology
MH  - Gap Junctions/physiology
MH  - Gene Expression
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Animal
MH  - Motor Neurons/pathology
MH  - Myelin P0 Protein/genetics
MH  - Myelin Sheath/*metabolism/pathology
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Schwann Cells/*metabolism
MH  - Gap Junction beta-1 Protein
PMC - PMC6725992
EDAT- 2005/02/11 09:00
MHDA- 2005/09/27 09:00
PMCR- 2005/08/09
CRDT- 2005/02/11 09:00
PHST- 2005/02/11 09:00 [pubmed]
PHST- 2005/09/27 09:00 [medline]
PHST- 2005/02/11 09:00 [entrez]
PHST- 2005/08/09 00:00 [pmc-release]
AID - 25/6/1550 [pii]
AID - 10.1523/JNEUROSCI.3082-04.2005 [doi]
PST - ppublish
SO  - J Neurosci. 2005 Feb 9;25(6):1550-9. doi: 10.1523/JNEUROSCI.3082-04.2005.