PMID- 19369543
OWN - NLM
STAT- MEDLINE
DCOM- 20090512
LR  - 20231213
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 15
DP  - 2009 Apr 15
TI  - Connexin32 mutations cause loss of function in Schwann cells and oligodendrocytes 
      leading to PNS and CNS myelination defects.
PG  - 4736-49
LID - 10.1523/JNEUROSCI.0325-09.2009 [doi]
AB  - The gap junction (GJ) protein connexin32 (Cx32) is expressed by myelinating 
      Schwann cells and oligodendrocytes and is mutated in X-linked Charcot-Marie-Tooth 
      disease. In addition to a demyelinating peripheral neuropathy, some Cx32 mutants 
      are associated with transient or chronic CNS phenotypes. To investigate the 
      molecular basis of these phenotypes, we generated transgenic mice expressing the 
      T55I or the R75W mutation and an IRES-EGFP, driven by the mouse Cnp promoter. The 
      transgene was expressed in oligodendrocytes throughout the CNS and in Schwann 
      cells. Both the T55I and the R75W mutants were localized in the perinuclear 
      cytoplasm, did not form GJ plaques, and did not alter the expression or 
      localization of two other oligodendrocytic GJ proteins, Cx47 and Cx29, or the 
      expression of Cx29 in Schwann cells. On wild type background, the expression of 
      endogenous mCx32 was unaffected by the T55I mutant, but was partly impaired by 
      R75W. Transgenic mice with the R75W mutation and all mutant animals with 
      Gjb1-null background developed a progressive demyelinating peripheral neuropathy 
      along with CNS myelination defects. These findings suggest that Cx32 mutations 
      result in loss of function in myelinated cells without trans-dominant effects on 
      other GJ proteins. Loss of Cx32 function alone in the CNS causes myelination 
      defects.
FAU - Sargiannidou, Irene
AU  - Sargiannidou I
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics, 1683 
      Nicosia, Cyprus.
FAU - Vavlitou, Natalie
AU  - Vavlitou N
FAU - Aristodemou, Sophia
AU  - Aristodemou S
FAU - Hadjisavvas, Andreas
AU  - Hadjisavvas A
FAU - Kyriacou, Kyriacos
AU  - Kyriacou K
FAU - Scherer, Steven S
AU  - Scherer SS
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
LA  - eng
GR  - R01 NS055284/NS/NINDS NIH HHS/United States
GR  - R01 NS055284-03/NS/NINDS NIH HHS/United States
GR  - R01 NS55284/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Central Nervous System/metabolism/*pathology/physiopathology
MH  - Connexins/*genetics/physiology
MH  - Demyelinating Diseases/*genetics/*pathology/physiopathology
MH  - Female
MH  - Genes, Dominant
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - *Mutagenesis, Site-Directed
MH  - Nerve Fibers, Myelinated/metabolism/pathology
MH  - Oligodendroglia/metabolism/*pathology
MH  - Peripheral Nervous System/metabolism/*pathology
MH  - Peripheral Nervous System Diseases/genetics/pathology/physiopathology
MH  - Schwann Cells/metabolism/*pathology
MH  - Gap Junction beta-1 Protein
PMC - PMC2721059
MID - NIHMS109788
EDAT- 2009/04/17 09:00
MHDA- 2009/05/13 09:00
PMCR- 2009/10/15
CRDT- 2009/04/17 09:00
PHST- 2009/04/17 09:00 [entrez]
PHST- 2009/04/17 09:00 [pubmed]
PHST- 2009/05/13 09:00 [medline]
PHST- 2009/10/15 00:00 [pmc-release]
AID - 29/15/4736 [pii]
AID - 3475790 [pii]
AID - 10.1523/JNEUROSCI.0325-09.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Apr 15;29(15):4736-49. doi: 10.1523/JNEUROSCI.0325-09.2009.