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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| Institution: | (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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