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Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors
journal contribution
posted on 2023-06-07, 23:49 authored by Alfons Rüsch, Lily Ng, Richard GoodyearRichard Goodyear, Dominik Oliver, Igor Lisoukov, Björn Vennström, Guy Richardson, Matthew W Kelley, Douglas ForrestThe 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.
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- Published
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- Published version
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Journal of NeuroscienceISSN
0270-6474Issue
24Volume
21Page range
9792-9800Pages
9.0Department affiliated with
- Neuroscience Publications
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- Yes
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- Yes
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2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-08-17Usage metrics
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