{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:08:04Z","timestamp":1781827684694,"version":"3.54.5"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,7,20]]},"abstract":"<jats:p>\n                    A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by\n                    <jats:italic>endothelin receptor type<\/jats:italic>\n                    <jats:italic>B<\/jats:italic>\n                    and\n                    <jats:italic>SOX10<\/jats:italic>\n                    has been reported. Despite the fact that c-\n                    <jats:italic>RET<\/jats:italic>\n                    is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-\n                    <jats:italic>Ret<\/jats:italic>\n                    and c-\n                    <jats:italic>RET<\/jats:italic>\n                    cause congenital deafness in mice and humans. Here, we show that impaired phosphorylation of c-Ret at tyrosine 1062 causes HSCR-linked syndromic congenital deafness in c-\n                    <jats:italic>Ret<\/jats:italic>\n                    knockin (KI) mice. The deafness involves neurodegeneration of spiral ganglion neurons (SGNs) with not only impaired phosphorylation of Akt and NF-\u03baB but decreased expression of calbindin D28k in inner ears. The congenital deafness involving neurodegeneration of SGNs in c-\n                    <jats:italic>Ret<\/jats:italic>\n                    KI mice was rescued by introducing constitutively activated RET. Taken together with our results for three patients with congenital deafness with c-\n                    <jats:italic>RET<\/jats:italic>\n                    \u2013mediated severe HSCR, our results indicate that c-\n                    <jats:italic>Ret<\/jats:italic>\n                    and c-\n                    <jats:italic>RET<\/jats:italic>\n                    are a deafness-related molecule in mice and humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1004520107","type":"journal-article","created":{"date-parts":[[2010,6,29]],"date-time":"2010-06-29T22:02:40Z","timestamp":1277848960000},"page":"13051-13056","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["c-Ret\u2013mediated hearing loss in mice with Hirschsprung disease"],"prefix":"10.1073","volume":"107","author":[{"given":"Nobutaka","family":"Ohgami","sequence":"first","affiliation":[{"name":"Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiru","family":"Ida-Eto","sequence":"additional","affiliation":[{"name":"Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shimotake","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, 920-8530, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Sakashita","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiko","family":"Sone","sequence":"additional","affiliation":[{"name":"Departments of dOtorhinolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Departments of dOtorhinolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Tabuchi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomofumi","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuyoshi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Aichi, 480-0392, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyonori","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nagoya Daini Red Cross Hospital, Nagoya, 466-8650, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Speech Pathology and Audiology, Aichi Gakuin University School of Health Science, Nisshin, Aichi, 470-0195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[{"name":"Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Jijiwa","sequence":"additional","affiliation":[{"name":"Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Asai","sequence":"additional","affiliation":[{"name":"Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kato","sequence":"additional","affiliation":[{"name":"Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,6,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"683","volume-title":"CURRENT Diagnosis and Treatment in Otolaryngology\u2014Head and Neck Surgery","author":"Lalwani AK","year":"2008","unstructured":"AK Lalwani, N G\u00fcrtler, Sensorineural hearing loss, the aging inner ear, and hereditary hearing impairment. 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