title: Deafness in TRbeta mutants is caused by malformation of the tectorial membrane.
abstract: Thyroid hormone receptor beta (TRbeta) dysfunction leads to deafness in humans and mice. Deafness in TRbeta(-/-) mutant mice has been attributed to TRbeta-mediated control of voltage- and Ca(2+)-activated K(+) (BK) channel expression in inner hair cells (IHCs). However, normal hearing in young constitutive BKalpha(-/-) mutants contradicts this hypothesis. Here, we show that mice with hair cell-specific deletion of TRbeta after postnatal day 11 (P11) have a delay in BKalpha expression but normal hearing, indicating that the origin of hearing loss in TRbeta(-/-) mutant mice manifested before P11. Analyzing the phenotype of IHCs in constitutive TRbeta(-/-) mice, we found normal Ca(2+) current amplitudes, exocytosis, and shape of compound action potential waveforms. In contrast, reduced distortion product otoacoustic emissions and cochlear microphonics associated with an abnormal structure of the tectorial membrane and enhanced tectorin levels suggest that disturbed mechanical performance is the primary cause of deafness resulting from TRbeta deficiency.
authors.affiliation: Department of Otorhinolaryngology, Tübingen Hearing Research Center, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Winter
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kuhn
authors.forename: Niels
authors.initials: N
authors.lastname: Brandt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hirt
authors.forename: Andreas
authors.initials: A
authors.lastname: Bress
authors.forename: Matthias
authors.initials: M
authors.lastname: Sausbier
authors.forename: Aude
authors.initials: A
authors.lastname: Conscience
authors.forename: Frederic
authors.initials: F
authors.lastname: Flamant
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Hubert
authors.initials: H
authors.lastname: Löwenheim
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001309:Auditory Threshold / Q000502:physiology; D003638:Deafness / Q000235:genetics* / Q000473:pathology*; D005089:Exocytosis / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism*; D013680:Tectorial Membrane / Q000503:physiopathology*; D037042:Thyroid Hormone Receptors beta / Q000172:deficiency*
chemical_list: D008565:Membrane Proteins; D024681:Potassium Channels, Calcium-Activated; D037042:Thyroid Hormone Receptors beta; C111170:tectonin I; C111171:tectonin II