title: A deafness-associated mutant human connexin 26 improves the epithelial barrier in vitro.
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.
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Queen Mary University of London, 4 Newark Street, Whitechapel, London, UK.
authors.forename: Y K Stella
authors.initials: YK
authors.lastname: Man
authors.forename: Caroline
authors.initials: C
authors.lastname: Trolove
authors.forename: Daniel
authors.initials: D
authors.lastname: Tattersall
authors.forename: Anna C
authors.initials: AC
authors.lastname: Thomas
authors.forename: Annie
authors.initials: A
authors.lastname: Papakonstantinopoulou
authors.forename: Drashnika
authors.initials: D
authors.lastname: Patel
authors.forename: Claire
authors.initials: C
authors.lastname: Scott
authors.forename: Jiehan
authors.initials: J
authors.lastname: Chong
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jagger
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: Harshad
authors.initials: H
authors.lastname: Navsaria
authors.forename: Michael A
authors.initials: MA
authors.lastname: Curtis
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009924:Organ Culture Techniques; D010957:Plasmids; D012763:Shigella flexneri / Q000472:pathogenicity
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26