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

• DOI: 10.1007/s00232-007-9025-0
• Publication Date: 2007-06-20T16:22:20Z
• Authors: Y. K. Stella Man; Caroline Trolove; Daniel Tattersall; Anna C. Thomas; Annie Papakonstan...; Drashnika Patel; Claire Scott; Jiehan Chong; Daniel J. Jagger; Edel A. O’Toole; Harshad Navsaria; Michael A. Curtis; David P. Kelsell
• Keywords: Keratinocytes; 0303 health sciences; Fluorescent Antibody Technique; Cell Differentiation; Epithelial Cells; Deafness; Coculture Techniques; Connexins; Shigella flexneri; Connexin 26; 03 medical and health sciences; Organ Culture Techniques; Cell Movement; Mutation; Humans; Cell Proliferation; HeLa Cells; Plasmids

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.