A Deafness-Associated Mutant Human Connexin 26 Improves the Epithelial Barrier In Vitro |
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| Authors: | Y. K. Stella Man Caroline Trolove Daniel Tattersall Anna C. Thomas Annie Papakonstantinopoulou Drashnika Patel Claire Scott Jiehan Chong Daniel J. Jagger Edel A. O’Toole Harshad Navsaria Michael A. Curtis David P. Kelsell |
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| Affiliation: | (1) Centre for Cutaneous Research, Institute of Cell and Molecular Science, Queen Mary University of London, 4 Newark Street, Whitechapel, London, E1 2AT, United Kingdom;(2) Centre for Infectious Diseases, Institute of Cell and Molecular Science, Queen Mary University of London, Whitechapel, London, E1 2AT, United Kingdom;(3) Centre for Auditory Research, UCL Ear Institute, University College London, London, WC1X 8EE, United Kingdom |
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| 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. The first two authors contributed equally to this work. |
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| Keywords: | Connexin 26 Deafness Epithelial barrier |
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