{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:44:24Z","timestamp":1790502264021,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives\/Hypothesis<\/jats:title>\n                    <jats:p>Intracellular entry of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) depends on the interaction between its spike protein with the cellular receptor angiotensin\u2010converting enzyme 2 (ACE2) and depends on Furin\u2010mediated spike protein cleavage and spike protein priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). As the expression of ACE2, TMPRSS2, and Furin in the middle and inner ear remain unclear, we analyzed the expression of these proteins in mouse ear tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Animal Research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed immunohistochemical analysis to examine the distribution of ACE2, TMPRSS2, and Furin in the Eustachian tube, middle ear spaces, and cochlea of mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ACE2 was present in the nucleus of the epithelium of the middle ear and Eustachian tube, as well as in some nuclei of the hair cells in the organ of Corti, in the stria vascularis, and the spiral ganglion cells. ACE2 was also expressed in the cytoplasm of the stria vascularis. TMPRSS2 was expressed in both the nucleus and cytoplasm in the middle spaces, with the expression being stronger in the nucleus in the mucosal epithelium of the middle ear spaces and Eustachian tube. TMPRSS2 was present in the cytoplasm in the organ of Corti and stria vascularis and in the nucleus and cytoplasm in the spiral ganglion. Furin was expressed in the cytoplasm in the middle ear spaces, Eustachian tube, and cochlea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ACE2, TMPRSS2, and Furin are diffusely present in the Eustachian tube, middle ear spaces, and cochlea, suggesting that these tissues are susceptible to SARS\u2010CoV\u20102 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>\n                      NA\n                      <jats:italic>Laryngoscope<\/jats:italic>\n                      , 131:E2013\u2013E2017, 2021\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.29324","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T13:50:39Z","timestamp":1607608239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Expression of\n                    <scp>ACE2<\/scp>\n                    ,\n                    <scp>TMPRSS2<\/scp>\n                    , and Furin in Mouse Ear Tissue, and the Implications for\n                    <scp>SARS\u2010CoV<\/scp>\n                    \u20102 Infection"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9346-6456","authenticated-orcid":false,"given":"Tsukasa","family":"Uranaka","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-9813","authenticated-orcid":false,"given":"Akinori","family":"Kashio","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-7237","authenticated-orcid":false,"given":"Rumi","family":"Ueha","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-1425","authenticated-orcid":false,"given":"Taku","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Bing","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-7232","authenticated-orcid":false,"given":"Makoto","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-5067","authenticated-orcid":false,"given":"Kenji","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-0973","authenticated-orcid":false,"given":"Tatsuya","family":"Yamasoba","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.34172\/aim.2020.09"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-020-05965-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26204"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2020.1922"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102487"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102473"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.06.023"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.14639\/0392-100X-N0820"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.05.034"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.20105114"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104742"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2002589117"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20617"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200404290-00013"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2007.11.022"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161084"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm934"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","unstructured":"R.Ueha K.Kondo R.Kagoya et al.Background mechanisms of olfactory dysfunction in COVID\u201019: expression of ACE2 TMPRSS2 and Furin in the nose and olfactory bulb in human and mice. Submittedhttps:\/\/biorxiv.org\/cgi\/content\/short\/2020.05.15.097352v1","DOI":"10.1101\/2020.05.15.097352"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.29324","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.29324","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.29324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T01:08:30Z","timestamp":1698109710000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.29324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,11]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/lary.29324"],"URL":"https:\/\/doi.org\/10.1002\/lary.29324","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.23.164335","asserted-by":"object"}]},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,11]]},"assertion":[{"value":"2020-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}