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Thyroid hormone receptor β is essential for development of auditory function

Nature Genetics volume 13, pages 354–357 (1996)Cite this article

Abstract

Congenital thyroid disorders are often associated with profound deafness, indicating a requirement for thyroid hormone (T3) and its receptors in the development of hearing1–5. Two T3 receptor genes, Trα and Trβ6,7, are differentially expressed, although in overlapping patterns, during development8–11. Thus, the extent to which they mediate unique or redundant functions is unclear. We demonstrate that Trβ-deficient (Thrb−/−) mice12 exhibit a permanent deficit in auditory function across a wide range of frequencies, although they show no other overt neurological defects. The auditory-evoked brainstem response (ABR) in Thrb−/− mice, although greatly diminished, displayed normal waveforms, which suggested that the primary defect resides in the cochlea. Although hypothyroidism causes cochlear malformation13,14, there was no evidence of this in Thrb−/− mice. These findings suggest that Trβ controls the maturation of auditory function but not morphogenesis of the cochlea. Thrb−/− mice provide a model for the human endocrine disorder of resistance to thyroid hormone (RTH), which is typically associated with dominant mutations in Trβ12,15. However, deafness is generally absent in RTH, indicating that dominant and recessive mutations in Trβ have different consequences on the auditory system. Our results identify Trβ as an essential transcription factor for auditory development and indicate that distinct Tr genes serve certain unique functions.

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Authors and Affiliations

  1. Department of Human Genetics, Mount Sinai School of Medicine, 5th Ave. at 100th St., New York, New York, 10029, USA

    Douglas Forrest & Lily Ng

  2. Department of Biological Sciences, University of Cincinnati, P.O. Box 210006, Cincinnati, Ohio, 45221, USA

    Lawrence C. Erway

  3. Kresge Hearing Research Institute, University of Michigan, 1301 E. Ann St., Ann Arbor, Michigan, 48109, USA

    Richard Altschuler

  4. Department of Developmental Neurobiology, St Judes Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Tom Curran

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Correspondence to Douglas Forrest.

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Forrest, D., Erway, L., Ng, L. et al. Thyroid hormone receptor β is essential for development of auditory function. Nat Genet 13, 354–357 (1996). https://doi.org/10.1038/ng0796-354

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