{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:51:53Z","timestamp":1790747513511,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010836","name":"American Laryngological, Rhinological and Otological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30 AR069655"],"award-info":[{"award-number":["P30 AR069655"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1K08 DC019416"],"award-info":[{"award-number":["1K08 DC019416"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the <jats:italic>Fmr1<\/jats:italic> gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the <jats:italic>Fmr1\u2010<\/jats:italic> knock\u2010out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the <jats:italic>Fmr1<\/jats:italic>\u2010KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA was isolated from cochlear nuclei of <jats:italic>Fmr1<\/jats:italic>\u2010KO and WT mice. Using next\u2010generation sequencing (RNA\u2010seq), the transcriptomes of <jats:italic>Fmr1<\/jats:italic>\u2010KO mice and WT mice (<jats:italic>n<\/jats:italic>\u2009=\u20093 each) were compared and analyzed using gene ontology programs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 270 unique, differentially expressed genes between <jats:italic>Fmr1<\/jats:italic>\u2010KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, <jats:italic>Kcnab2<\/jats:italic>, which encodes a subunit of the Shaker voltage\u2010gated potassium channel, is expressed at an abnormally low level in the <jats:italic>Fmr1<\/jats:italic>\u2010KO cochlear nucleus. <jats:italic>Kcnab2<\/jats:italic> and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>N\/A <jats:italic>Laryngoscope<\/jats:italic>, 134:1363\u20131371, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30936","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T11:45:48Z","timestamp":1691495148000},"page":"1363-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-8352","authenticated-orcid":false,"given":"Hitomi","family":"Sakano","sequence":"first","affiliation":[{"name":"Department of Otolaryngology University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Neuroscience University of Rochester Medical Center  Rochester New York USA"},{"name":"Center for RNA Biology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-1903","authenticated-orcid":false,"given":"Michael S.","family":"Castle","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paromita","family":"Kundu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3379"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.10.1038"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90283-5"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.059055"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00019"},{"key":"e_1_2_7_7_1","first-page":"23","article-title":"Fmr1 knockout mice: a model to study fragile X mental retardation. 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