Abstract
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.
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Acknowledgements
This work was funded by the Research Advisory Board of Barts and the London, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust to D. P. K. We express special thanks to Dr. Jash Vyas for advice and help with the migration assays and Professor Tom MacDonald for the normal human colon and help with interpretation of Cx26 localization.
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Man, Y.K.S., Trolove, C., Tattersall, D. et al. A Deafness-Associated Mutant Human Connexin 26 Improves the Epithelial Barrier In Vitro . J Membrane Biol 218, 29–37 (2007). https://doi.org/10.1007/s00232-007-9025-0
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DOI: https://doi.org/10.1007/s00232-007-9025-0