biostudies-literatureWinter HNIDCD NIH HHSNCI NIH HHS2581-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC2748340biostudies-literatureUnknown29(8)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.The Journal of neuroscience : the official journal of the Society for NeuroscienceDeafness in TRbeta mutants is caused by malformation of the tectorial membrane.PMC2748340P30 CA021765-31P30 CA021765DC06471DC05168R21 DC005168-03DC008800R01 DC006471R21 DC005168R21 DC008800R01 DC006471-06CA21765R21 DC008800-02Muller MFlamant FRuttiger LSausbier MBrandt NConscience ALowenheim HEngel JRuth PZimmermann UKnipper MZuo JSamarut JWinter HPfister MTian YKuhn SBress AHirt BfalseDeafness in TRbeta mutants is caused by malformation of the tectorial membrane.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.2009-01-01T00:00:00Z2009 Feb2020-08-20T07:09:13Z2019-03-27T00:25:11ZS-EPMC27483401924453410.1523/JNEUROSCI.3557-08.200910.1523/jneurosci.3557-08.2009