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Sellitto C, Li L, White TW. Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome. Sci Rep. 2021;11(1):24118doi: 10.1038/s41598-021-03627-8.
Sellitto, C., Li, L., & White, T. W. (2021). Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome. Scientific reports, 11(1), 24118. https://doi.org/10.1038/s41598-021-03627-8
Sellitto, Caterina, et al. "Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome." Scientific reports vol. 11,1 (2021): 24118. doi: https://doi.org/10.1038/s41598-021-03627-8
Sellitto C, Li L, White TW. Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome. Sci Rep. 2021 Dec 16;11(1):24118. doi: 10.1038/s41598-021-03627-8. PMID: 34916582; PMCID: PMC8677806.
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Sci Rep. 2021 Dec 16;11(1):24118. doi: 10.1038/s41598-021-03627-8.

Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome.

Scientific reports

Caterina Sellitto, Leping Li, Thomas W White

Affiliations

  1. Department of Physiology and Biophysics, Stony Brook University, T5-147, Basic Science Tower, Stony Brook, NY, 11794-8661, USA.
  2. Department of Physiology and Biophysics, Stony Brook University, T5-147, Basic Science Tower, Stony Brook, NY, 11794-8661, USA. [email protected].

PMID: 34916582 PMCID: PMC8677806 DOI: 10.1038/s41598-021-03627-8

Abstract

Mutations in five different genes encoding connexin channels cause eleven clinically defined human skin diseases. Keratitis ichthyosis deafness (KID) syndrome is caused by point mutations in the GJB2 gene encoding Connexin 26 (Cx26) which result in aberrant activation of connexin hemichannels. KID syndrome has no cure and is associated with bilateral hearing loss, blinding keratitis, palmoplantar keratoderma, ichthyosiform erythroderma and a high incidence of childhood mortality. Here, we have tested whether a topically applied hemichhanel inhibitor (flufenamic acid, FFA) could ameliorate the skin pathology associated with KID syndrome in a transgenic mouse model expressing the lethal Cx26-G45E mutation. We found that FFA blocked the hemichannel activity of Cx26-G45E in vitro, and substantially reduced epidermal pathology in vivo, compared to untreated, or vehicle treated control animals. FFA did not reduce the expression of mutant connexin hemichannel protein, and cessation of FFA treatment allowed disease progression to continue. These results suggested that aberrant hemichannel activity is a major driver of skin disease in KID syndrome, and that the inhibition of mutant hemichannel activity could provide an attractive target to develop novel therapeutic interventions to treat this incurable disease.

© 2021. The Author(s).

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