{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:08:37Z","timestamp":1789189717727,"version":"build-2803163510"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Zhejiang Province","award":["2018C03026"],"award-info":[{"award-number":["2018C03026"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81330024"],"award-info":[{"award-number":["81330024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31671305"],"award-info":[{"award-number":["31671305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31701082"],"award-info":[{"award-number":["31701082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81600817"],"award-info":[{"award-number":["81600817"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key Research and Development Program of China","award":["2018YFC1004802"],"award-info":[{"award-number":["2018YFC1004802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,3]]},"abstract":"<jats:p>\n                    The pathophysiology underlying spiral ganglion cell defect\u2013induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative\n                    <jats:italic>MAP1B<\/jats:italic>\n                    gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous\n                    <jats:italic>MAP1B<\/jats:italic>\n                    mutations (c.4198A&gt;G, p.1400S&gt;G; c.2768T&gt;C, p.923I&gt;T; c.5512T&gt;C, p.1838F&gt;L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that\n                    <jats:italic>MAP1B<\/jats:italic>\n                    is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron\u2013like cells, generated by pluripotent stem cells from patients carrying the\n                    <jats:italic>MAP1B<\/jats:italic>\n                    mutation and control subject, we demonstrated that the p.1400S&gt;G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron\u2013like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron\u2013like cells were rescued by genetically correcting\n                    <jats:italic>MAP1B<\/jats:italic>\n                    mutation using CRISPR\/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of\n                    <jats:italic>Map1b<\/jats:italic>\n                    heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from\n                    <jats:italic>Map1b<\/jats:italic>\n                    mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules.\n                    <jats:italic>Map1b<\/jats:italic>\n                    deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.136046","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T11:01:27Z","timestamp":1606906887000},"source":"Crossref","is-referenced-by-count":31,"title":["Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss"],"prefix":"10.1172","volume":"5","author":[{"given":"Limei","family":"Cui","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"},{"name":"Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"},{"name":"Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5114-6048","authenticated-orcid":true,"given":"Hanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghua","family":"Peng","sequence":"additional","affiliation":[{"name":"Deaprtment of Otorhinolaryngology, the Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiufen","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankai","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick A.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology, University of California at San Diego School of Medicine, La Jolla California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"},{"name":"Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-6736","authenticated-orcid":true,"given":"Min-Xin","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital,"},{"name":"Institute of Genetics and"},{"name":"Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."},{"name":"Division of Otolaryngology, University of California at San Diego School of Medicine, La Jolla California, USA."},{"name":"Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Hangzhou, Zhejiang, China."},{"name":"Joint Institute of Genetics and Genomic Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"9","key":"B1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a033258","article-title":"The Epidemiology of Deafness","volume":"9","author":"Sheffield","year":"2018","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31073-5"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.10.1229"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-012110-142228"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.10.006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy158"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/63.1.73"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2002.620101.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050428"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215113003265"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/387080a0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80556-5"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/3118"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-60"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.01.007"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128691"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22178"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001439"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.76"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2011.10.003"},{"issue":"Pt 14","key":"B21","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1242\/jcs.040162","article-title":"Nonprimed and DYRK1A-primed GSK3 beta-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons","volume":"122","author":"Scales","year":"2009","journal-title":"J Cell Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.72"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5294"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-05-01712.1989"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nature03487"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20013"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12576"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.07.011"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7317"},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2017.00021","article-title":"Signaling and Transcription Factors during Inner Ear Development: The Generation of Hair Cells and Otic Neurons","volume":"5","author":"Galvez","year":"2017","journal-title":"Front Cell Dev Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490320407"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2016.01.001"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621225114"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0901-11.2011"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03609.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.6.2085"},{"issue":"Pt 10","key":"B37","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1093\/brain\/awt153","article-title":"Beyond taxol: microtubule-based treatment of disease and injury of the nervous system","volume":"136","author":"Baas","year":"2013","journal-title":"Brain"},{"key":"B38","article-title":"Overview of methods for assessing the mouse auditory system","volume":"Chapter 8","author":"Willott","year":"2006","journal-title":"Curr Protoc Neurosci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e318282964f"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69041417.x"},{"issue":"Pt 23","key":"B41","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1242\/jcs.114.23.4273","article-title":"Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3beta is induced during PC12 cell differentiation","volume":"114","author":"Goold","year":"2001","journal-title":"J Cell Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5080-09.2010"},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2015.00343","article-title":"Neurodegeneration and microtubule dynamics: death by a thousand cuts","volume":"9","author":"Dubey","year":"2015","journal-title":"Front Cell Neurosci"},{"issue":"Pt 3","key":"B44","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.brainresbull.2016.06.016","article-title":"Microtubules in health and degenerative disease of the nervous system","volume":"126","author":"Matamoros","year":"2016","journal-title":"Brain Res Bull"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.130061"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx440"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008826"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09074-4"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100219"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1086\/381133"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv498"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134965"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.16"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nature11415"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000317"},{"key":"B57","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/B978-0-12-801185-0.00015-5","article-title":"CRISPR\/Cas9-based genome editing in mice by single plasmid injection","volume":"546","author":"Fujihara","year":"2014","journal-title":"Methods Enzymol"},{"issue":"116","key":"B58","doi-asserted-by":"crossref","DOI":"10.3791\/54538","article-title":"Spiral Ganglion Neuron Explant Culture and Electrophysiology on Multi Electrode Arrays","author":"Hahnewald","year":"2016","journal-title":"J Vis Exp"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0252"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/136046\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:50:12Z","timestamp":1779151812000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/136046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":59,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12,3]]},"published-print":{"date-parts":[[2020,12,3]]}},"alternative-id":["10.1172\/jci.insight.136046"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.136046","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]},"article-number":"e136046"}}