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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ng L,Goodyear RJ,Woods CA,Schneider MJ,Diamond E,Richardson GP,Kelley MW,Germain DL,Galton VA,Forrest Ddoi
10.1073/pnas.0307402101keywords:
subject
Has Abstractpub_date
2004-03-09 00:00:00pages
3474-9issue
10eissn
0027-8424issn
1091-6490pii
0307402101journal_volume
101pub_type
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