{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:09:00Z","timestamp":1780524540165,"version":"3.54.1"},"reference-count":133,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","award":["K7013_B3413"],"award-info":[{"award-number":["K7013_B3413"]}],"id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asociaci\u00f3n S\u00edndrome de Meniere Espa\u00f1a (ASMES)","award":["K7013_B3413"],"award-info":[{"award-number":["K7013_B3413"]}]},{"name":"Meniere\u2019s Society, UK","award":["K7013_B3413"],"award-info":[{"award-number":["K7013_B3413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Meniere\u2019s disease (MD) is a set of rare disorders that affects &gt;4 million people worldwide. Individuals with MD suffer from episodes of vertigo associated with fluctuating sensorineural hearing loss and tinnitus. Hearing loss can involve one or both ears. Over 10% of the reported cases are observed in families, suggesting its significant genetic contribution. The condition is polygenic with &gt;20 genes, and several patterns of inheritance have been reported, including autosomal dominant, autosomal recessive, and digenic inheritance across multiple MD families. Preclinical research using animal models has been an indispensable tool for studying the neurophysiology of the auditory and vestibular systems and to get a better understanding of the functional role of genes that are involved in the hearing and vestibular dysfunction. While mouse models are the most used preclinical model, this review analyzes alternative animal and non-animal models that can be used to study MD genes. Methods: A literature search of the 21 genes reported for familial MD and the preclinical models used to investigate their functional role was performed. Results: Comparing the homology of proteins encoded by these genes to other model organisms revealed Drosophila and zebrafish as cost-effective models to screen multiple genes and study the pathophysiology of MD. Conclusions: Murine models are preferred for a quantitative neurophysiological assessment of hearing and vestibular functions to develop drug or gene therapy.<\/jats:p>","DOI":"10.3390\/jcm14051427","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T11:03:37Z","timestamp":1740049417000},"page":"1427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical Models to Study the Molecular Pathophysiology of Meniere\u2019s Disease: A Pathway to Gene Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-9069","authenticated-orcid":false,"given":"Prathamesh T.","family":"Nadar-Ponniah","sequence":"first","affiliation":[{"name":"Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose A.","family":"Lopez-Escamez","sequence":"additional","affiliation":[{"name":"Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2065, Australia"},{"name":"Otology & Neurotology Group CTS495, Division of Otolaryngology, Department of Surgery, Instituto de Investigaci\u00f3n Biosanitaria, ibs.GRANADA, Universidad de Granada, 18071 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10162-023-00896-0","article-title":"Types of Inheritance and Genes Associated with Familial Meniere Disease","volume":"24","year":"2023","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.12703\/r\/12-11","article-title":"Recent advances in understanding molecular bases of Meniere\u2019s disease","volume":"12","author":"Frejo","year":"2023","journal-title":"Fac. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41435-024-00260-z","article-title":"Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease","volume":"25","author":"Flook","year":"2024","journal-title":"Genes. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110413","DOI":"10.1016\/j.clim.2024.110413","article-title":"Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease: A longitudinal study","volume":"271","author":"Frejo","year":"2024","journal-title":"Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1002\/ohn.386","article-title":"Immune-Related Disorders Associated With Meniere\u2019s Disease: A Systematic Review and Meta-analysis","volume":"169","author":"Vela","year":"2023","journal-title":"Otolaryngol. Head. Neck. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41420-024-02246-2","article-title":"IL-1beta promotes glutamate excitotoxicity: Indications for the link between inflammatory and synaptic vesicle cycle in Meniere\u2019s disease","volume":"10","author":"Zhang","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, M.H. (2022). Population-based study for the comorbidities and associated factors in Meniere\u2019s disease. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-12492-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/cge.12150","article-title":"Aran Familial clustering and genetic heterogeneity in Meniere\u2019s disease","volume":"85","author":"Requena","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1177\/000348944905800303","article-title":"The factor of heredity in labyrinthine deafness and paroxysmal vertigo; Meniere\u2019s syndrome","volume":"58","author":"Brown","year":"1949","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1177\/000348946507400408","article-title":"Occurrence of episodic vertigo and hearing loss in families","volume":"74","author":"Bernstein","year":"1965","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1017\/S0022215108002788","article-title":"Familial Meniere\u2019s disease: Clinical and genetic aspects","volume":"123","author":"Morrison","year":"2009","journal-title":"J. Laryngol. Otol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1002\/lary.25207","article-title":"Genetic aspects and clinical characteristics of familial Meniere\u2019s disease in a South Korean population","volume":"125","author":"Lee","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ejhg.2016.154","article-title":"Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere\u2019s disease","volume":"25","author":"Requena","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1001\/jamaoto.2021.4282","article-title":"Pathogenesis and Etiology of Meniere Disease: A Scoping Review of a Century of Evidence","volume":"148","author":"Rizk","year":"2022","journal-title":"JAMA Otolaryngol. Head. Neck Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.7874\/jao.2020.00115","article-title":"Experimental Animal Models for Meniere\u2019s Disease: A Mini-Review","volume":"24","author":"Seo","year":"2020","journal-title":"J. Audiol. Otol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(99)00180-X","article-title":"Endolymphatic hydrops induced by chronic administration of vasopressin","volume":"140","author":"Takeda","year":"2000","journal-title":"Hear Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3109\/00016489.2013.771282","article-title":"The effect of systemic administration of desmopressin on cochlear function in guinea pigs","volume":"133","author":"Chihara","year":"2013","journal-title":"Acta Otolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/000348947508400301","article-title":"Effect of fistulae on endolymphatic hydrops","volume":"84","author":"Kimura","year":"1975","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/MOO.0000000000001002","article-title":"Update on the pathophysiology, diagnosis and management of Meniere\u2019s disease","volume":"32","year":"2024","journal-title":"Curr. Opin. Otolaryngol. Head. Neck Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3233\/VES-200786","article-title":"Imaging of endolymphatic hydrops: A comprehensive update in primary and secondary hydropic ear disease","volume":"31","author":"Eliezer","year":"2021","journal-title":"J. Vestib. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lamolda, M., Frejo, L., Gallego-Martinez, A., and Lopez-Escamez, J.A. (2023). Application of Human Stem Cells to Model Genetic Sensorineural Hearing Loss and Meniere Disease. Cells, 12.","DOI":"10.20944\/preprints202302.0321.v1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112623","DOI":"10.1016\/j.celrep.2023.112623","article-title":"A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs","volume":"42","author":"Steinhart","year":"2023","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25948","DOI":"10.1073\/pnas.1902781116","article-title":"Otogelin, otogelin-like, and stereocilin form links connecting outer hair cell stereocilia to each other and the tectorial membrane","volume":"116","author":"Avan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0378-5955(01)00312-4","article-title":"Spatiotemporal expression of otogelin in the developing and adult mouse inner ear","volume":"158","author":"Petit","year":"2001","journal-title":"Hear Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1387\/ijdb.072364de","article-title":"Development of Johnston\u2019s organ in Drosophila","volume":"51","author":"Eberl","year":"2007","journal-title":"Int. J. Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/wdev.128","article-title":"The Drosophila auditory system","volume":"3","author":"Eberl","year":"2014","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/ng1622","article-title":"Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway","volume":"37","author":"Wang","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dmm031492","DOI":"10.1242\/dmm.031492","article-title":"Using Drosophila to study mechanisms of hereditary hearing loss","volume":"11","author":"Li","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/dneu.22221","article-title":"Hearing molecules, mechanism and transportation: Modeled in Drosophila melanogaster","volume":"75","author":"Bokolia","year":"2015","journal-title":"Dev. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.semcdb.2013.03.010","article-title":"The role of Atonal transcription factors in the development of mechanosensitive cells","volume":"24","author":"Jarman","year":"2013","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.conb.2015.02.001","article-title":"Hearing in Drosophila","volume":"34","author":"Albert","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/0092-8674(93)90358-W","article-title":"atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system","volume":"73","author":"Jarman","year":"1993","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/369398a0","article-title":"Atonal is the proneural gene for Drosophila photoreceptors","volume":"369","author":"Jarman","year":"1994","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ydbio.2013.06.022","article-title":"Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear","volume":"381","author":"Chonko","year":"2013","journal-title":"Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2012.06.043","article-title":"Drosophila auditory organ genes and genetic hearing defects","volume":"150","author":"Senthilan","year":"2012","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ogienko, A.A., Omelina, E.S., Bylino, O.V., Batin, M.A., Georgiev, P.G., and Pindyurin, A.V. (2022). Drosophila as a Model Organism to Study Basic Mechanisms of Longevity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911244"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cub.2005.03.050","article-title":"Myosin VIIA defects, which underlie the Usher 1B syndrome in humans, lead to deafness in Drosophila","volume":"15","author":"Todi","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_38","first-page":"82","article-title":"Chronic hemorrhagic pleural effusion in mediastinal pancreatic pseudocyst","volume":"80","author":"Lehnert","year":"1991","journal-title":"Schweiz Rundsch Med. Prax"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0168-9525(89)90103-0","article-title":"Genetics and early development of zebrafish","volume":"5","author":"Kimmel","year":"1989","journal-title":"Trends Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/291293a0","article-title":"Production of clones of homozygous diploid zebra fish (Brachydanio rerio)","volume":"291","author":"Streisinger","year":"1981","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1089\/zeb.2015.1166","article-title":"Hearing Assessment in Zebrafish During the First Week Postfertilization","volume":"13","author":"Yao","year":"2016","journal-title":"Zebrafish"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Inoue, M., Tanimoto, M., and Oda, Y. (2013). The role of ear stone size in hair cell acoustic sensory transduction. Sci. Rep., 3.","DOI":"10.1038\/srep02114"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/1097-4695(20000615)43:4<329::AID-NEU2>3.0.CO;2-H","article-title":"Development of utricular otoliths, but not saccular otoliths, is necessary for vestibular function and survival in zebrafish","volume":"43","author":"Riley","year":"2000","journal-title":"J. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/neu.10123","article-title":"Zebrafish as a model for hearing and deafness","volume":"53","author":"Whitfield","year":"2002","journal-title":"J. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Manley, G.A., Fay, R.R., and Popper, A.N. (2004). Evolution of Sensory Hair Cells. Evolution of the Vertebrate Auditory System, Springer.","DOI":"10.1007\/978-1-4419-8957-4"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1146\/annurev.genet.39.073003.105049","article-title":"The genetics of hearing and balance in zebrafish","volume":"39","author":"Nicolson","year":"2005","journal-title":"Annu. Rev. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1113\/jphysiol.2013.265108","article-title":"In vivo and in vitro biophysical properties of hair cells from the lateral line and inner ear of developing and adult zebrafish","volume":"592","author":"Olt","year":"2014","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1242\/jeb.01534","article-title":"Development of the acoustically evoked behavioral response in zebrafish to pure tones","volume":"208","author":"Zeddies","year":"2005","journal-title":"J. Exp. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10162-012-0349-9","article-title":"Evolutionary paths to mammalian cochleae","volume":"13","author":"Manley","year":"2012","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e82978","DOI":"10.7554\/eLife.82978","article-title":"Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes","volume":"12","author":"Shi","year":"2023","journal-title":"eLife"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/dvdy.10073","article-title":"Development of the zebrafish inner ear","volume":"223","author":"Whitfield","year":"2002","journal-title":"Dev. Dyn."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.heares.2016.09.004","article-title":"Hearing sensitivity differs between zebrafish lines used in auditory research","volume":"341","author":"Monroe","year":"2016","journal-title":"Hear. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10162-021-00798-z","article-title":"How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research","volume":"22","author":"Sheets","year":"2021","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/zeb.2021.0063","article-title":"The Sound World of Zebrafish: A Critical Review of Hearing Assessment","volume":"19","author":"Popper","year":"2022","journal-title":"Zebrafish"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.heares.2005.05.005","article-title":"The use of zebrafish for assessing ototoxic and otoprotective agents","volume":"208","author":"Ton","year":"2005","journal-title":"Hear. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/hmg\/ddu524","article-title":"Identification of two novel mutations in FAM136A and DTNA genes in autosomal-dominant familial Meniere\u2019s disease","volume":"24","author":"Requena","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.modgep.2004.01.015","article-title":"Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse development","volume":"4","author":"Lien","year":"2004","journal-title":"Gene Expr. Patterns"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41592-021-01200-9","article-title":"gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration","volume":"18","author":"Orvis","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Requena, T., Keder, A., Lage, P.Z., Albert, J.T., and Jarman, A.P. (2022). A Drosophila model for Meniere\u2019s disease: Dystrobrevin is required for support cell function in hearing and proprioception. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1015651"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1093\/hmg\/ddw183","article-title":"A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere\u2019s disease","volume":"25","author":"Requena","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1093\/hmg\/ddl022","article-title":"Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction","volume":"15","author":"Robertson","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1007\/s00405-015-3885-1","article-title":"Distinct vestibular phenotypes in DFNA9 families with COCH variants","volume":"273","author":"Kim","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Escalera-Balsera, A., Roman-Naranjo, P., and Lopez-Escamez, J.A. (2020). Systematic Review of Sequencing Studies and Gene Expression Profiling in Familial Meniere Disease. Genes, 11.","DOI":"10.3390\/genes11121414"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-6448-2_1","article-title":"Semaphorins and their Signaling Mechanisms","volume":"1493","author":"Alto","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1136\/jmedgenet-2019-106159","article-title":"Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere\u2019s disease","volume":"57","author":"Requena","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Requena, T., Gallego-Martinez, A., and Lopez-Escamez, J.A. (2018). Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00108"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"a033514","DOI":"10.1101\/cshperspect.a033514","article-title":"The Tectorial Membrane: Mechanical Properties and Functions","volume":"9","author":"Sellon","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_68","first-page":"211","article-title":"Alpha-tectorin involvement in hearing disabilities: One gene--two phenotypes","volume":"105","author":"Balciuniene","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E4853","DOI":"10.1073\/pnas.1720121115","article-title":"Osmotic stabilization prevents cochlear synaptopathy after blast trauma","volume":"115","author":"Kim","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e829","DOI":"10.1002\/ctm2.829","article-title":"Defective alpha-tectorin may involve tectorial membrane in familial Meniere disease","volume":"12","author":"Aran","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Lacerda, L., and Alves, S. (2012). Glycosaminoglycan storage disorders: A review. Biochem. Res. Int., 2012.","DOI":"10.1155\/2012\/471325"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/humu.20828","article-title":"Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome)","volume":"30","author":"Tomatsu","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wolfberg, J., Chintalapati, K., Tomatsu, S., and Nagao, K. (2020). Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions. Diagnostics, 10.","DOI":"10.3390\/diagnostics10080554"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0378-5955(02)00341-6","article-title":"Inner ear pathology in the mucopolysaccharidosis VII mouse","volume":"169","author":"Ohlemiller","year":"2002","journal-title":"Hear Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Skarp, S., Korvala, J., Kotim\u00e4ki, J., Sorri, M., M\u00e4nnikk\u00f6, M., and Hietikko, E. (2022). New Genetic Variants in CYP2B6 and SLC6A Support the Role of Oxidative Stress in Familial Meniere\u2019s Disease. Genes, 13.","DOI":"10.3390\/genes13060998"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/cmi.2014.81","article-title":"Extracellular pattern recognition molecules in health and diseases","volume":"12","author":"Zhang","year":"2015","journal-title":"Cell Mol. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1080\/00016489.2019.1663365","article-title":"Solute carrier family 4 member 1 might participate in the pathogenesis of Meniere\u2019s disease in a murine endolymphatic hydrop model","volume":"139","author":"Sun","year":"2019","journal-title":"Acta Otolaryngol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1001\/archotol.134.4.403","article-title":"A novel SLC26A4 (PDS) deafness mutation retained in the endoplasmic reticulum","volume":"134","author":"Brownstein","year":"2008","journal-title":"Arch. Otolaryngol. Head. Neck Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1476-5381.2012.01975.x","article-title":"The solute carrier 6 family of transporters","volume":"167","author":"Broer","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"111974","DOI":"10.1016\/j.ecoenv.2021.111974","article-title":"Ammonia exposure induces oxidative stress and inflammation by destroying the microtubule structures and the balance of solute carriers in the trachea of pigs","volume":"212","author":"Wang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13073-024-01425-1","article-title":"A rare haplotype of the GJD3 gene segregating in familial Meniere\u2019s disease interferes with connexin assembly","volume":"17","author":"Chua","year":"2025","journal-title":"Genome Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/cne.22509","article-title":"Stereocilin connects outer hair cell stereocilia to one another and to the tectorial membrane","volume":"519","author":"Verpy","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/ajmg.a.34391","article-title":"Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major contributor to pediatric bilateral sensorineural hearing impairment","volume":"158A","author":"Francey","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss","volume":"135","author":"Bierer","year":"2016","journal-title":"Hum Genet"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/cge.12332","article-title":"DFNB16 is a frequent cause of congenital hearing impairment: Implementation of STRC mutation analysis in routine diagnostics","volume":"87","author":"Vona","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Yokota, Y., Moteki, H., Nishio, S.-Y., Yamaguchi, T., Wakui, K., Kobayashi, Y., Ohyama, K., Miyazaki, H., Matsuoka, R., and Abe, S. (2019). Frequency and clinical features of hearing loss caused by STRC deletions. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40586-7"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1038\/s41431-018-0256-6","article-title":"Stereocilin gene variants associated with episodic vertigo: Expansion of the DFNB16 phenotype","volume":"26","author":"Frykholm","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.devcel.2004.06.016","article-title":"Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx","volume":"7","author":"Wang","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ydbio.2009.12.028","article-title":"Pivotal role of hmx2 and hmx3 in zebrafish inner ear and lateral line development","volume":"339","author":"Feng","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.yexcr.2005.03.016","article-title":"Hmx homeobox gene function in inner ear and nervous system cell-type specification and development","volume":"306","author":"Wang","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41467-023-44316-6","article-title":"TMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress","volume":"15","author":"Jeong","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_92","first-page":"89","article-title":"Gene mapping of a nonsyndromic hearing impairmint family","volume":"20","author":"Cheng","year":"2003","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/72793","article-title":"Targeted disruption of otog results in deafness and severe imbalance","volume":"24","author":"Simmler","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"14450","DOI":"10.1073\/pnas.94.26.14450","article-title":"Otogelin: A glycoprotein specific to the acellular membranes of the inner ear","volume":"94","author":"Leibovici","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1097\/AUD.0000000000000878","article-title":"Burden of Rare Variants in the OTOG Gene in Familial Meniere\u2019s Disease","volume":"41","author":"Aran","year":"2020","journal-title":"Ear Hear."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.ajhg.2012.09.012","article-title":"Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment","volume":"91","author":"Schraders","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0896-6273(89)90265-1","article-title":"A membrane glycoprotein associated with the limbic system mediates the formation of the septo-hippocampal pathway in vitro","volume":"3","author":"Keller","year":"1989","journal-title":"Neuron"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"319","DOI":"10.34172\/aim.2020.21","article-title":"Limbic System Associated Membrane Protein Mutation in an Iranian Family Diagnosed with Meniere\u2019s Disease","volume":"23","author":"Mehrjoo","year":"2020","journal-title":"Arch. Iran. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e18312","DOI":"10.7554\/eLife.18312","article-title":"PDZD7-MYO7A complex identified in enriched stereocilia membranes","volume":"5","author":"Morgan","year":"2016","journal-title":"eLife"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12688\/wellcomeopenres.17428.2","article-title":"Immunohistochemistry localises myosin-7a to cochlear efferent boutons","volume":"7","author":"Sirko","year":"2022","journal-title":"Wellcome Open Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41467-020-14288-y","article-title":"Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts","volume":"11","author":"Cirulli","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"108329","DOI":"10.1016\/j.heares.2021.108329","article-title":"Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease","volume":"409","author":"Moleon","year":"2021","journal-title":"Hear. Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Xie, B., Liang, J., Jiang, J., Zeng, T., Liu, L., Xie, D., Zhu, G., Xiong, L., Zhang, K., and Liu, D. (2024). Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1405109"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1093\/hmg\/9.14.2189","article-title":"Mariner is defective in myosin VIIA: A zebrafish model for human hereditary deafness","volume":"9","author":"Ernest","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41467-020-20864-z","article-title":"A binding protein regulates myosin-7a dimerization and actin bundle assembly","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0896-6273(01)00397-X","article-title":"A novel gene causing a mendelian audiogenic mouse epilepsy","volume":"31","author":"Skradski","year":"2001","journal-title":"Neuron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1210\/mend.14.9.0511","article-title":"Sequence similarities between a novel putative G protein-coupled receptor and Na+\/Ca2+ exchangers define a cation binding domain","volume":"14","author":"Nikkila","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_108","first-page":"1102","article-title":"Intraorbital ophthalmic artery aneurysm: Case report","volume":"31","author":"Ogawa","year":"1992","journal-title":"Neurosurgery"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1523\/JNEUROSCI.0693-06.2006","article-title":"The very large G-protein-coupled receptor VLGR1: A component of the ankle link complex required for the normal development of auditory hair bundles","volume":"26","author":"McGee","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6478","DOI":"10.1523\/JNEUROSCI.0342-07.2007","article-title":"Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning","volume":"27","author":"Michalski","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e2205993","DOI":"10.1002\/advs.202205993","article-title":"Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment","volume":"10","author":"Guan","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1086\/381685","article-title":"Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II","volume":"74","author":"Weston","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1159\/000491068","article-title":"A Natural Occurring Mouse Model with Adgrv1 Mutation of Usher Syndrome 2C and Characterization of its Recombinant Inbred Strains","volume":"47","author":"Yan","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Stemerdink, M., Broekman, S., Peters, T., Kremer, H., de Vrieze, E., and van Wijk, E. (2023). Generation and Characterization of a Zebrafish Model for ADGRV1-Associated Retinal Dysfunction Using CRISPR\/Cas9 Genome Editing Technology. Cells, 12.","DOI":"10.3390\/cells12121598"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ceb.2008.06.004","article-title":"Cadherins and mechanotransduction by hair cells","volume":"20","author":"Muller","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1530\/ror.0.0050053","article-title":"Cadherins: Crucial regulators of structure and function in reproductive tissues","volume":"5","author":"Rowlands","year":"2000","journal-title":"Rev. Reprod."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/83667","article-title":"Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D","volume":"27","author":"Bolz","year":"2001","journal-title":"Nat Genet"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1086\/316954","article-title":"Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23","volume":"68","author":"Bork","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Johnson, K.R., Tian, C., Gagnon, L.H., Jiang, H., Ding, D., and Salvi, R. (2017). Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL\/6 and 129S1\/Sv mice and comparisons with congenic strains. Sci. Rep., 7.","DOI":"10.1038\/srep44450"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1006\/geno.2001.6554","article-title":"Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice","volume":"74","author":"Wilson","year":"2001","journal-title":"Genomics"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.gene.2012.01.084","article-title":"A mutation in the cdh23 gene causes age-related hearing loss in Cdh23(nmf308\/nmf308) mice","volume":"499","author":"Liu","year":"2012","journal-title":"Gene"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.1073\/pnas.0900691106","article-title":"A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells","volume":"106","author":"Schwander","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yang, S., Xie, B.-L., Dong, X.-P., Wang, L.-X., Zhu, G.-H., Wang, T., Wu, W.-J., Lai, R.-S., Tao, R., and Guan, M.-X. (2023). cdh23 affects congenital hearing loss through regulating purine metabolism. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1079529"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1093\/hmg\/ddg358","article-title":"PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23","volume":"12","author":"Ahmed","year":"2003","journal-title":"Hum Mol Genet"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Yoshimura, H., Iwasaki, S., Nishio, S.-Y., Kumakawa, K., Tono, T., Kobayashi, Y., Sato, H., Nagai, K., Ishikawa, K., and Ikezono, T. (2014). Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090688"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"dmm048965","DOI":"10.1242\/dmm.048965","article-title":"Usher syndrome type 1-associated gene, pcdh15b, is required for photoreceptor structural integrity in zebrafish","volume":"14","author":"Miles","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1083\/jcb.200507072","article-title":"Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli","volume":"171","author":"Tran","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1093\/emboj\/cdf689","article-title":"Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle","volume":"21","author":"Bahloul","year":"2002","journal-title":"EMBO J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00439-002-0732-4","article-title":"Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC","volume":"110","author":"Ahmed","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00439-002-0736-0","article-title":"Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness","volume":"111","author":"Ouyang","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1242\/dmm.006429","article-title":"Harmonin (Ush1c) is required in zebrafish Muller glial cells for photoreceptor synaptic development and function","volume":"4","author":"Phillips","year":"2011","journal-title":"Dis. Model. Mech."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1523\/JNEUROSCI.2267-16.2016","article-title":"Global Analysis of Protein Expression of Inner Ear Hair Cells","volume":"37","author":"Hickox","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1242\/jcs.002568","article-title":"Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions","volume":"120","author":"Etournay","year":"2007","journal-title":"J. Cell Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:39:04Z","timestamp":1760027944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":133,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051427"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051427","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]}}}