Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase

Ng, Lily, Goodyear, Richard J, Woods, Chad A, Schneider, Mark J, Diamond, Edward, Richardson, Guy P, Kelley, Matthew W, St Germain, Donald L, Galton, Valerie Anne and Forrest, Douglas (2004) Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proceedings of the National Academy of Sciences, 101 (10). pp. 3474-3479. ISSN 0027-8424

Full text not available from this repository.

Abstract

The later stages of cochlear differentiation and the developmental onset of hearing require thyroid hormone. Although thyroid hormone receptors (TRs) are a prerequisite for this process, it is likely that other factors modify TR activity during cochlear development. The mouse cochlea expresses type 2 deiodinase (D2), an enzyme that converts thyroxine, the main form of thyroid hormone in the circulation, into 3,5,3'-triiodothyronine (T3) the major ligand for TRs. Here, we show that D2-deficient mice have circulating thyroid hormone levels that would normally be adequate to allow hearing to develop but they exhibit an auditory phenotype similar to that caused by systemic hypothyroidism or TR deletions. D2-deficient mice have defective auditory function, retarded differentiation of the cochlear inner sulcus and sensory epithelium, and deformity of the tectorial membrane. The similarity of this phenotype to that caused by TR deletions suggests that D2 controls the T3 signal that activates TRs in the cochlea. Thus, D2 is essential for hearing, and the results suggest that this hormone-activating enzyme confers on the cochlea the ability to stimulate its own T3 response at a critical developmental period.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Richard Goodyear
Date Deposited: 06 Feb 2012 18:29
Last Modified: 21 May 2012 15:36
URI: http://srodev.sussex.ac.uk/id/eprint/16711
📧 Request an update