{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:14:57Z","timestamp":1791947697138,"version":"4.3.4"},"reference-count":73,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T00:00:00Z","timestamp":1248739200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2009,1,28]]},"abstract":"<jats:p>The absence of thyroid hormone (TH) during late gestation and early infancy can cause irreparable deafness in both humans and rodents. A variety of rodent models have been used in an effort to identify the underlying molecular mechanism. Here, we characterize a mouse model of secondary hypothyroidism, pituitary transcription factor 1 (<jats:italic>Pit1<\/jats:italic><jats:sup>dw<\/jats:sup>), which has profound, congenital deafness that is rescued by oral TH replacement. These mutants have tectorial membrane abnormalities, including a prominent Hensen's stripe, elevated \u03b2-tectorin composition, and disrupted striated-sheet matrix. They lack distortion product otoacoustic emissions and cochlear microphonic responses, and exhibit reduced endocochlear potentials, suggesting defects in outer hair cell function and potassium recycling. Auditory system and hair cell physiology, histology, and anatomy studies reveal novel defects of hormone deficiency related to deafness: (1) permanently impaired expression of KCNJ10 in the stria vascularis of<jats:italic>Pit1<\/jats:italic><jats:sup>dw<\/jats:sup>mice, which likely contributes to the reduced endocochlear potential, (2) significant outer hair cell loss in the mutants, which may result from cellular stress induced by the lower KCNQ4 expression and current levels in<jats:italic>Pit1<\/jats:italic><jats:sup>dw<\/jats:sup>mutant outer hair cells, and (3) sensory and strial cell deterioration, which may have implications for thyroid hormone dysregulation in age-related hearing impairment. In summary, we suggest that these defects in outer hair cell and strial cell function are important contributors to the hearing impairment in<jats:italic>Pit1<\/jats:italic><jats:sup>dw<\/jats:sup>mice.<\/jats:p>","DOI":"10.1523\/jneurosci.4957-08.2009","type":"journal-article","created":{"date-parts":[[2009,1,28]],"date-time":"2009-01-28T18:28:38Z","timestamp":1233167318000},"page":"1212-1223","source":"Crossref","is-referenced-by-count":72,"title":["Deafness and Permanently Reduced Potassium Channel Gene Expression and Function in Hypothyroid<i>Pit1<\/i><sup>dw<\/sup>Mutants"],"prefix":"10.1523","volume":"29","author":[{"given":"Mirna","family":"Mustapha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzy-Wen","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Dolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehoash","family":"Raphael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Camper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Keith","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2009,1,28]]},"reference":[{"key":"2023041303362764000_29.4.1212.1","doi-asserted-by":"publisher","DOI":"10.1086\/345398"},{"key":"2023041303362764000_29.4.1212.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-007-9004-5"},{"key":"2023041303362764000_29.4.1212.3","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0411"},{"key":"2023041303362764000_29.4.1212.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2110-05.2005"},{"key":"2023041303362764000_29.4.1212.5","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026515619443"},{"key":"2023041303362764000_29.4.1212.6","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(90)90200-9"},{"key":"2023041303362764000_29.4.1212.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3965-06.2007"},{"key":"2023041303362764000_29.4.1212.8","doi-asserted-by":"publisher","DOI":"10.1038\/384033a0"},{"key":"2023041303362764000_29.4.1212.9","doi-asserted-by":"crossref","first-page":"7630","DOI":"10.1523\/JNEUROSCI.21-19-07630.2001","article-title":"Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice","volume":"21","author":"Camarero","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303362764000_29.4.1212.10","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90050-5"},{"key":"2023041303362764000_29.4.1212.11","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10620"},{"key":"2023041303362764000_29.4.1212.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04584.x"},{"key":"2023041303362764000_29.4.1212.13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.069559"},{"key":"2023041303362764000_29.4.1212.14","doi-asserted-by":"publisher","DOI":"10.1159\/000076000"},{"key":"2023041303362764000_29.4.1212.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.02.028"},{"key":"2023041303362764000_29.4.1212.16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0140-6736(73)93310-2","article-title":"Congenital deafness and hypothyroidism","volume":"2","author":"Deol","year":"1973","journal-title":"Lancet"},{"key":"2023041303362764000_29.4.1212.17","doi-asserted-by":"crossref","unstructured":"Eichhoff G Busche MA Garaschuk O (2008) In vivo calcium imaging of the aging and diseased brain. Eur J Nucl Med Mol Imaging (Suppl 1):S99\u2013S106.","DOI":"10.1007\/s00259-007-0709-6"},{"key":"2023041303362764000_29.4.1212.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(03)00032-9"},{"key":"2023041303362764000_29.4.1212.19","doi-asserted-by":"publisher","DOI":"10.1210\/me.10.12.1570"},{"key":"2023041303362764000_29.4.1212.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700356104"},{"key":"2023041303362764000_29.4.1212.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng0793-227"},{"key":"2023041303362764000_29.4.1212.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1640-04.2004"},{"key":"2023041303362764000_29.4.1212.23","doi-asserted-by":"publisher","DOI":"10.1007\/s003470050496"},{"key":"2023041303362764000_29.4.1212.24","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1016\/S0006-3495(93)81248-7","article-title":"Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation","volume":"65","author":"Huang","year":"1993","journal-title":"Biophys J"},{"key":"2023041303362764000_29.4.1212.25","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-4-37"},{"key":"2023041303362764000_29.4.1212.26","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1460-9568.2007.05994.x","article-title":"Spatiotemporal loss of K+ transport proteins in the developing cochlear lateral wall of guinea pigs with hereditary deafness","volume":"27","author":"Jin","year":"2008","journal-title":"Eur J Neurosci"},{"key":"2023041303362764000_29.4.1212.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(02)96858-8"},{"key":"2023041303362764000_29.4.1212.28","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-007-9038-0"},{"key":"2023041303362764000_29.4.1212.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00058-1"},{"key":"2023041303362764000_29.4.1212.30","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600951"},{"key":"2023041303362764000_29.4.1212.31","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1242\/dev.125.18.3709","article-title":"Thyroid hormone affects Schwann cell and oligodendrocyte gene expression at the glial transition zone of the VIIIth nerve prior to cochlea function","volume":"125","author":"Knipper","year":"1998","journal-title":"Development"},{"key":"2023041303362764000_29.4.1212.32","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1152\/jn.2000.83.5.3101","article-title":"Thyroid hormone deficiency before the onset of hearing causes irreversible damage to peripheral and central auditory systems","volume":"83","author":"Knipper","year":"2000","journal-title":"J Neurophysiol"},{"key":"2023041303362764000_29.4.1212.33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103385200"},{"key":"2023041303362764000_29.4.1212.34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.116889"},{"key":"2023041303362764000_29.4.1212.35","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/BF03345237","article-title":"Ageing, growth hormone and physical performance","volume":"26","author":"Lanfranco","year":"2003","journal-title":"J Endocrinol Invest"},{"key":"2023041303362764000_29.4.1212.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00102-1"},{"key":"2023041303362764000_29.4.1212.37","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(00)00349-0"},{"key":"2023041303362764000_29.4.1212.38","doi-asserted-by":"publisher","DOI":"10.1038\/nn1496"},{"key":"2023041303362764000_29.4.1212.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2006.08.003"},{"key":"2023041303362764000_29.4.1212.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00150-1"},{"key":"2023041303362764000_29.4.1212.41","doi-asserted-by":"publisher","DOI":"10.1038\/347528a0"},{"key":"2023041303362764000_29.4.1212.42","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1242\/dev.129.14.3523","article-title":"Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene","volume":"129","author":"Li","year":"2002","journal-title":"Development"},{"key":"2023041303362764000_29.4.1212.43","doi-asserted-by":"publisher","DOI":"10.1038\/nature01059"},{"key":"2023041303362764000_29.4.1212.44","doi-asserted-by":"publisher","DOI":"10.1038\/364208a0"},{"key":"2023041303362764000_29.4.1212.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00653.x"},{"key":"2023041303362764000_29.4.1212.46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00312.2001"},{"key":"2023041303362764000_29.4.1212.47","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-007-0083-x"},{"key":"2023041303362764000_29.4.1212.48","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1177\/019459987908700617","article-title":"Electron microscopic findings in presbycusic degeneration of the basal turn of the human cochlea","volume":"87","author":"Nadol","year":"1979","journal-title":"Otolaryngol Head Neck Surg"},{"key":"2023041303362764000_29.4.1212.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.186"},{"key":"2023041303362764000_29.4.1212.50","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02715.x"},{"key":"2023041303362764000_29.4.1212.51","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0791n.x"},{"key":"2023041303362764000_29.4.1212.52","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(89)90090-7"},{"key":"2023041303362764000_29.4.1212.53","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32830e20c4"},{"key":"2023041303362764000_29.4.1212.54","doi-asserted-by":"publisher","DOI":"10.1097\/01.mao.0000169764.00798.84"},{"key":"2023041303362764000_29.4.1212.55","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(02)00799-2"},{"key":"2023041303362764000_29.4.1212.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(03)00009-9"},{"key":"2023041303362764000_29.4.1212.57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15758"},{"key":"2023041303362764000_29.4.1212.58","doi-asserted-by":"crossref","first-page":"9792","DOI":"10.1523\/JNEUROSCI.21-24-09792.2001","article-title":"Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors","volume":"21","author":"Rusch","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303362764000_29.4.1212.59","doi-asserted-by":"publisher","DOI":"10.1038\/nn1828"},{"key":"2023041303362764000_29.4.1212.60","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1311"},{"key":"2023041303362764000_29.4.1212.61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3974-06.2007"},{"key":"2023041303362764000_29.4.1212.62","doi-asserted-by":"publisher","DOI":"10.1038\/72793"},{"key":"2023041303362764000_29.4.1212.63","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-008-0140-0"},{"key":"2023041303362764000_29.4.1212.64","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/00016488609122726","article-title":"Periods of sensitivity to thyroid hormone during the development of the organ of Corti","volume":"429","author":"Uziel","year":"1986","journal-title":"Acta Otolaryngol Suppl"},{"key":"2023041303362764000_29.4.1212.65","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(83)90079-5"},{"key":"2023041303362764000_29.4.1212.66","doi-asserted-by":"publisher","DOI":"10.1136\/adc.58.6.419"},{"key":"2023041303362764000_29.4.1212.67","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20375"},{"key":"2023041303362764000_29.4.1212.68","first-page":"361","article-title":"Deafness in myxoedema","volume":"48","author":"Van't Hoff","year":"1979","journal-title":"Q J Med"},{"key":"2023041303362764000_29.4.1212.69","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-2-30"},{"key":"2023041303362764000_29.4.1212.70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052609899"},{"key":"2023041303362764000_29.4.1212.71","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03013"},{"key":"2023041303362764000_29.4.1212.72","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-351X(96)80500-3"},{"key":"2023041303362764000_29.4.1212.73","doi-asserted-by":"publisher","DOI":"10.1038\/35012009"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.4957-08.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T19:06:41Z","timestamp":1681412801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.4957-08.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1,28]]},"references-count":73,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2009,1,28]]},"published-print":{"date-parts":[[2009,1,28]]}},"alternative-id":["10.1523\/JNEUROSCI.4957-08.2009"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.4957-08.2009","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1,28]]}}}