Deafness in TRβ Mutants Is Caused by Malformation of the Tectorial Membrane

Thyroid hormone receptor beta(TR beta) dysfunction leads to deafness in humans and mice. Deafness in TR beta(-/-) mutant mice has been attributed to TR beta-mediated control of voltage- and Ca2+-activated K+ (BK) channel expression in inner hair cells (IHCs). However, normal hearing in young constitutive BK alpha(-/-) mutants contradicts this hypothesis. Here, we show that mice with hair cell-specific deletion of TR beta after postnatal day 11 (P11) have a delay in BK alpha expression but normal hearing, indicating that the origin of hearing loss in TR beta(-/-) mutant mice manifested before P11. Analyzing the phenotype of IHCs in constitutive TR beta(-/-) mice, we found normal Ca2(+) 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 TR beta deficiency.