PMID- 19876648
OWN - NLM
STAT- MEDLINE
DCOM- 20100212
LR  - 20211020
IS  - 1432-1203 (Electronic)
IS  - 0340-6717 (Linking)
VI  - 127
IP  - 2
DP  - 2010 Feb
TI  - A novel mutation in the connexin 29 gene may contribute to nonsyndromic hearing 
      loss.
PG  - 191-9
LID - 10.1007/s00439-009-0758-y [doi]
AB  - Connexins (Cxs) are homologous four-transmembrane domain proteins and constitute 
      the major components of gap junctions. Among a cohort of patients with 
      nonsyndromic hearing loss, we recently identified a novel missense mutation, 
      E269D, in the GJC3 gene encoding connexin 29 (Cx29), as being causally related to 
      hearing loss. The functional alteration of Cx29 caused by the mutant GJC3 gene, 
      however, remains unknown. This study compared the intracellular distribution and 
      assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in 
      HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed 
      continuous staining along apposed cell membranes in the fluorescent localization 
      assay. In contrast, the p.E269D missense mutation resulted in accumulation of the 
      Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the 
      cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a 
      bi-directional tet-on expression system demonstrated that the heteromeric 
      connexon accumulated in the cytoplasm, thereby impairing the formation of the gap 
      junction. Based on these findings, we suggest that Cx29E269D has a dominant 
      negative effect on the formation and function of the gap junction. These results 
      provide a novel molecular explanation for the role Cx29 plays in the development 
      of hearing loss.
FAU - Hong, Hui-Mei
AU  - Hong HM
AD  - Department of BioMedical Sciences, Chung Shan Medical University, Taichung, 
      Taiwan, ROC.
FAU - Yang, Jiann-Jou
AU  - Yang JJ
FAU - Su, Ching-Chyuan
AU  - Su CC
FAU - Chang, Juan-Yu
AU  - Chang JY
FAU - Li, Tung-Cheng
AU  - Li TC
FAU - Li, Shuan-Yow
AU  - Li SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091030
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Connexins)
RN  - 0 (GJC3 protein, human)
RN  - 0 (Mutant Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Cell Membrane/metabolism
MH  - Cell Survival
MH  - Connexins/chemistry/*genetics/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Gap Junctions/metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - HeLa Cells
MH  - Hearing Loss/*genetics/pathology
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Mutant Proteins/chemistry/genetics/metabolism
MH  - *Mutation, Missense
MH  - Nerve Tissue Proteins/chemistry/*genetics/metabolism
MH  - Protein Multimerization
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Transfection
EDAT- 2009/10/31 06:00
MHDA- 2010/02/13 06:00
CRDT- 2009/10/31 06:00
PHST- 2009/08/31 00:00 [received]
PHST- 2009/10/17 00:00 [accepted]
PHST- 2009/10/31 06:00 [entrez]
PHST- 2009/10/31 06:00 [pubmed]
PHST- 2010/02/13 06:00 [medline]
AID - 10.1007/s00439-009-0758-y [doi]
PST - ppublish
SO  - Hum Genet. 2010 Feb;127(2):191-9. doi: 10.1007/s00439-009-0758-y. Epub 2009 Oct 
      30.