TY - JOUR
T1 - Deafness in TRbeta mutants is caused by malformation of the tectorial membrane
AU - Winter, Harald
AU - Ruttiger, Lukas
AU - Muller, Marcus
AU - Kuhn, Stephanie
AU - Brandt, Niels
AU - Zimmermann, Ulrike
AU - Hirt, Bernard
AU - Bress, Andreas
AU - Sausbier, Matthias
AU - Conscience, Aude
AU - Flamant, Frederic
AU - Tian, Yong
AU - Zuo, Jian
AU - Pfister, Markus
AU - Ruth, Peter
AU - Lowenheim, Hubert
AU - Samarut, Jacques
AU - Engel, Jutta
AU - Knipper, Marlies
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19244534
M3 - Article
SN - 0270-6474
VL - 29
SP - 2581
EP - 2587
JO - The Journal of Neuroscience
JF - The Journal of Neuroscience
IS - 8
ER -