Deafness-Associated Mutant Human Connexin 26 Improves the Epithelial Barrier In Vitro

Deafness-Associated Mutant Human Connexin 26 Improves the Epithelial Barrier In Vitro

A large proportion of recessive nonsyndromic hearing loss is due to mutations in the GJB2 gene encoding connexin 26 (Cx26), a component of a gap junction. Within different ethnic groups there are specific common recessive mutations, each with a relatively high carrier frequency, suggesting the possi...

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Bibliographic Details
Published in:The Journal of membrane biology Vol. 218; no. 1-3; pp. 29 - 37
Main Authors: Man, Y. K. Stella, Trolove, Caroline, Tattersall, Daniel, Thomas, Anna C, Papakonstantinopoulou, Annie, Patel, Drashnika, Scott, Claire, Chong, Jiehan, Jagger, Daniel J, O'Toole, Edel A, Navsaria, Harshad, Curtis, Michael A, Kelsell, David P
Format: Journal Article
Language:English
Published: United States New York : Springer-Verlag 01-08-2007
Springer Nature B.V
Subjects:
Cell Differentiation
Cell Movement
Cell Proliferation
Cells
Coculture Techniques
Connexin 26
Connexins - genetics
Deafness
Deafness - genetics
Epithelial barrier
Epithelial Cells - metabolism
Fluorescent Antibody Technique
Gene loci
Genes
Genetic research
HeLa Cells - microbiology
Humans
Keratinocytes - cytology
Keratinocytes - metabolism
Mutation
Mutation - genetics
Organ Culture Techniques
Pathogens
Plasmids
Shigella flexneri - pathogenicity
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Summary:A large proportion of recessive nonsyndromic hearing loss is due to mutations in the GJB2 gene encoding connexin 26 (Cx26), a component of a gap junction. Within different ethnic groups there are specific common recessive mutations, each with a relatively high carrier frequency, suggesting the possibility of heterozygous advantage. Carriers of the R143W GJB2 allele, the most prevalent in the African population, present with a thicker epidermis than noncarriers. In this study, we show that (R143W)Cx26-expressing keratinocytes form a significantly thicker epidermis in an organotypic coculture skin model. In addition, we show increased migration of cells expressing (R143W)Cx26 compared to (WT)Cx26-overexpressing cells. We also demonstrate that cells expressing (R143W)Cx26 are significantly less susceptible to cellular invasion by the enteric pathogen Shigella flexneri than (WT)Cx26-expressing cells. These in vitro studies suggest an advantageous effect of (R143W)Cx26 in epithelial cells.
Bibliography:http://dx.doi.org/10.1007/s00232-007-9025-0
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The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
ISSN:0022-2631
1432-1424
DOI:10.1007/s00232-007-9025-0