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- Title
Deafness in TRβ Mutants Is Caused by Malformation of the Tectorial Membrane.
- Authors
Winter, Harald; Rüttiger, Lukas; Müller, Marcus; Kuhn, Stephanie; Brandt, Niels; Zimmermann, Ulrike; Hirt, Bernhard; Bress, Andreas; Sausbier, Matthias; Conscience, Aude; Flamant, Frederic; Yong Tian; Jian Zuo; Pfister, Markus; Ruth, Peter; Löwenheim, Hubert; Samarut, Jacques; Engel, Jutta; Knipper, Marlies
- Abstract
Thyroid hormone receptor β (TRβ) dysfunction leads to deafness in humans and mice. Deafness in TRβ-/- mutant mice has been attributed to TRβ-mediated control of voltage- and Ca2+-activated K+ (BK) channel expression in inner hair cells (IHCs). However, normal hearing in young constitutive BKα-/- mutants contradicts this hypothesis. Here, we show that mice with hair cell-specific deletion of TRβ after postnatal day 11 (P11) have a delay in BKα expression but normal hearing, indicating that the origin of hearing loss in TRβ-/- mutant mice manifested before P11. Analyzing the phenotype of IHCs in constitutive TRβ-/- 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 TRβ deficiency.
- Subjects
DEAFNESS; THYROID hormones; HORMONE receptors; HAIR cells; EXOCYTOSIS
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 8, p2581
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3557-08.2009