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There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cytoplasmic domains; they are thought to function redundantly in mechano\u2010electrical transduction during hair\u2010bundle development, but whether any of these isoforms composes the tip\u2010link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post\u2010natal hair cell\u2010specific conditional knockout mice (\n                    <jats:italic>Pcdh15<\/jats:italic>\n                    <jats:sup>ex38\u2010fl\/ex38\u2010fl<\/jats:sup>\n                    <jats:italic>Myo15<\/jats:italic>\n                    \u2010\n                    <jats:italic>cre<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ) that lose only this isoform after normal hair\u2010bundle development, we show that Pcdh15\u2010CD2 is an essential component of tip\u2010links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a\n                    <jats:italic>PCDH15<\/jats:italic>\n                    frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15\u2010CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano\u2010electrical transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by\n                    <jats:italic>PCDH15<\/jats:italic>\n                    defects.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201403976","type":"journal-article","created":{"date-parts":[[2014,6,18]],"date-time":"2014-06-18T02:34:23Z","timestamp":1403058863000},"page":"984-992","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["The CD2 isoform of protocadherin\u201015 is an essential component of the tip\u2010link complex in mature auditory hair cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Elise","family":"Pepermans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Goodyear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystel","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Abdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Typhaine","family":"Dupont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souad","family":"Gherbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Makrelouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Hardelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Marlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akila","family":"Zenati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Avan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Bahloul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,17]]},"reference":[{"key":"BFEMMM201403976_CR1","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1523\/JNEUROSCI.1163-06.2006","volume":"26","author":"ZM Ahmed","year":"2006","unstructured":"Ahmed ZM, Goodyear R, Riazuddin S, Lagziel A, Legan PK, Behra M, Burgess SM, Lilley KS, Wilcox ER, Riazuddin S et\u00a0al (2006) The tip\u2010link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin\u201015. 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