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Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis.
Proc Natl Acad Sci U S A. 2007 Apr 10; 104(15):6229-34.PN

Abstract

The endocochlear potential (EP) is essential to hearing, because it provides approximately half of the driving force for the mechanoelectrical transduction current in auditory hair cells. The EP is produced by the stria vascularis (SV), a vascularized bilayer epithelium of the cochlea lateral wall. The absence of the gap junction protein connexin30 (Cx30) in Cx30(-/-) mice results in the SV failure to produce an EP, which mainly accounts for the severe congenital hearing impairment of these mice. Here, we show that the SV components of the EP electrogenic machinery and the epithelial barriers limiting the intrastrial fluid space, which are both necessary for the EP production, were preserved in Cx30(-/-) mice. In contrast, the endothelial barrier of the capillaries supplying the SV was disrupted before EP onset. This disruption is expected to result in an intrastrial electric shunt that is sufficient to account for the absence of the EP production. Immunofluorescence analysis of wild-type mice detected Cx30 in the basal and intermediate cells of the SV but not in the endothelial cells of the SV capillaries. Moreover, dye-coupling experiments showed that endothelial cells were not coupled to the SV basal, intermediate, and marginal cells. SV transcriptome analysis revealed a significant down-regulation of betaine homocysteine S-methyltransferase (Bhmt) in the Cx30(-/-) mice, which was restricted to the SV and resulted in a local increase in homocysteine, a known factor of endothelial dysfunction. Disruption of the SV endothelial barrier is a previously undescribed pathogenic process underlying hearing impairment.

Authors+Show Affiliations

Unité de Génétique des Déficits Sensoriels, Unité Mixte de Recherche S 587, Institut National de la Santé et de la Recherche Médicale, 75724 Paris Cedex 15, France. martin.cohen-salmon@college-de-france.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17400755

Citation

Cohen-Salmon, Martine, et al. "Connexin30 Deficiency Causes Instrastrial Fluid-blood Barrier Disruption Within the Cochlear Stria Vascularis." Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 15, 2007, pp. 6229-34.
Cohen-Salmon M, Regnault B, Cayet N, et al. Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis. Proc Natl Acad Sci U S A. 2007;104(15):6229-34.
Cohen-Salmon, M., Regnault, B., Cayet, N., Caille, D., Demuth, K., Hardelin, J. P., Janel, N., Meda, P., & Petit, C. (2007). Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis. Proceedings of the National Academy of Sciences of the United States of America, 104(15), 6229-34.
Cohen-Salmon M, et al. Connexin30 Deficiency Causes Instrastrial Fluid-blood Barrier Disruption Within the Cochlear Stria Vascularis. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6229-34. PubMed PMID: 17400755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis. AU - Cohen-Salmon,Martine, AU - Regnault,Béatrice, AU - Cayet,Nadège, AU - Caille,Dorothée, AU - Demuth,Karine, AU - Hardelin,Jean-Pierre, AU - Janel,Nathalie, AU - Meda,Paolo, AU - Petit,Christine, Y1 - 2007/03/30/ PY - 2007/4/3/pubmed PY - 2007/10/18/medline PY - 2007/4/3/entrez SP - 6229 EP - 34 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 104 IS - 15 N2 - The endocochlear potential (EP) is essential to hearing, because it provides approximately half of the driving force for the mechanoelectrical transduction current in auditory hair cells. The EP is produced by the stria vascularis (SV), a vascularized bilayer epithelium of the cochlea lateral wall. The absence of the gap junction protein connexin30 (Cx30) in Cx30(-/-) mice results in the SV failure to produce an EP, which mainly accounts for the severe congenital hearing impairment of these mice. Here, we show that the SV components of the EP electrogenic machinery and the epithelial barriers limiting the intrastrial fluid space, which are both necessary for the EP production, were preserved in Cx30(-/-) mice. In contrast, the endothelial barrier of the capillaries supplying the SV was disrupted before EP onset. This disruption is expected to result in an intrastrial electric shunt that is sufficient to account for the absence of the EP production. Immunofluorescence analysis of wild-type mice detected Cx30 in the basal and intermediate cells of the SV but not in the endothelial cells of the SV capillaries. Moreover, dye-coupling experiments showed that endothelial cells were not coupled to the SV basal, intermediate, and marginal cells. SV transcriptome analysis revealed a significant down-regulation of betaine homocysteine S-methyltransferase (Bhmt) in the Cx30(-/-) mice, which was restricted to the SV and resulted in a local increase in homocysteine, a known factor of endothelial dysfunction. Disruption of the SV endothelial barrier is a previously undescribed pathogenic process underlying hearing impairment. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/17400755/Connexin30_deficiency_causes_instrastrial_fluid_blood_barrier_disruption_within_the_cochlear_stria_vascularis_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17400755 DB - PRIME DP - Unbound Medicine ER -