Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors

Rüsch, Alfons, Ng, Lily, Goodyear, Richard, Oliver, Dominik, Lisoukov, Igor, Vennström, Björn, Richardson, Guy, Kelley, Matthew W and Forrest, Douglas (2001) Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors. Journal of Neuroscience, 21 (24). pp. 9792-9800. ISSN 0270-6474

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Abstract

The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRa1 and TRß thyroid hormone receptors in the auditory system using receptor-deficient mice. TRa1 and TRß, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TRß is required for hearing because TRß-deficient (Thrb tm1/tm1) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (I K,f) in the cochlear inner hair cells. Here, we show that although TRa1 is individually dispensable, TRa1 and TRß synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrb tm1/tm1 mice, the deletion of all TRs inThra tm1/tm1 Thrb tm1/tm1mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction ofI K,f in inner hair cells was not markedly more retarded than in Thrb tm1/tm1mice, suggesting that this feature of hair cell maturation is primarily TRß-dependent. These results indicate that distinct pathways mediated by TRß alone or by TRß and TRa1 together facilitate control over an extended range of functions during the maturation of the cochlea.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Richard Goodyear
Date Deposited: 06 Feb 2012 19:43
Last Modified: 07 Mar 2017 04:43
URI: http://sro.sussex.ac.uk/id/eprint/21913

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