{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:44:27Z","timestamp":1789101867028,"version":"build-2803163510"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Gap junction (GJ) proteins, connexin26 and 30, are highly prevalent in the human cochlea (HC), where they are involved in transcellular signaling, metabolic supply, and fluid homeostasis. Their genes, <jats:italic>GJB2<\/jats:italic> and <jats:italic>GJB6<\/jats:italic>, are both located at the DFNB1 locus on chromosome 13q12. Mutations in <jats:italic>GJB2<\/jats:italic> may cause mild to profound non-syndromic deafness. Here, we analyzed for the first time the various expressions of <jats:italic>GJB2 and GJB6<\/jats:italic> gene transcripts in the different cell networks in the HC using the RNAscope technique.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Archival paraformaldehyde-fixed sections of surgically obtained HC were used to label single mRNA oligonucleotides using the sensitive multiplex RNAscope<jats:sup>\u00ae<\/jats:sup> technique with fluorescent-tagged probes. Positive and negative controls also included the localization of <jats:italic>ATP1A1<\/jats:italic>, <jats:italic>ATP1A2<\/jats:italic>, and KCNJ10 gene transcripts in order to validate the specificity of labeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Confocal and super-resolution structured illumination microscopy (SR-SIM) detected single gene transcripts as brightly stained puncta. The <jats:italic>GJB2<\/jats:italic> and <jats:italic>GJB6<\/jats:italic> gene transcripts were distributed in the epithelial and connective tissue systems in all three cochlear turns. The largest number of <jats:italic>GJB2<\/jats:italic> and <jats:italic>GJB6<\/jats:italic> gene transcripts was in the outer sulcus, spiral ligament, and stria vascularis (SV). Oligonucleotides were present in the supporting cells of the organ of Corti (OC), spiral limbus fibrocytes, and the floor of the scala vestibuli. Multiplex gene data suggest that cells in the cochlear lateral wall contain either <jats:italic>GJB2<\/jats:italic> or <jats:italic>GJB6<\/jats:italic> gene transcripts or both. The <jats:italic>GJB6<\/jats:italic>, but not <jats:italic>GJB2<\/jats:italic>, gene transcripts were found in the intermediate cells but none were found in the marginal cells. There were no <jats:italic>GJB2<\/jats:italic> or <jats:italic>GJB6<\/jats:italic> gene transcripts found in the hair cells and only a few in the spiral ganglion cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both <jats:italic>GJB2<\/jats:italic> and <jats:italic>GJB6<\/jats:italic> mRNA gene transcripts were localized in cells in the adult HC using RNAscope<jats:sup>\u00ae<\/jats:sup><jats:italic>in situ<\/jats:italic> hybridization (ISH) and high resolution microscopy. Generally, <jats:italic>GJB6<\/jats:italic> dominated over <jats:italic>GJB2<\/jats:italic>, except in the basal cells. Results suggest that cells may contain either <jats:italic>GJB2<\/jats:italic> or <jats:italic>GJB6<\/jats:italic> gene transcripts or both. This may be consistent with specialized GJ plaques having separate channel permeability and gating properties. A reduction in the number of <jats:italic>GJB2<\/jats:italic> gene transcripts was found in the basal turn. Such information may be useful for future gene therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2022.973646","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T08:13:13Z","timestamp":1663661593000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["GJB2 and GJB6 gene transcripts in the human cochlea: A study using RNAscope, confocal, and super-resolution structured illumination microscopy"],"prefix":"10.3389","volume":"15","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Rask-Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/S0006-291X(03)01166-5","article-title":"Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mice.","volume":"307","author":"Ahmad","year":"2003","journal-title":"Biochem. 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