Age-Related Hearing Loss and Degeneration of Cochlear Hair Cells in Mice Lacking Thyroid Hormone Receptor β1

A key function of the thyroid hormone receptor beta (Thrb) gene is in the development of auditory function. However, the roles of the 2 receptor isoforms, TR beta 1 and TR beta 2, expressed by the Thrb gene are unclear, and it is unknown whether these isoforms promote the maintenance as well as development of hearing. We investigated the function of TR beta 1 in mice with a Thrb(b1) reporter allele that expresses beta-galactosidase instead of TR beta 1. In the immature cochlea, beta-galactosidase was detected in the greater epithelial ridge, sensory hair cells, spiral ligament, and spiral ganglion and in adulthood, at low levels in the hair cells, support cells and root cells of the outer sulcus. Although deletion of all TR beta isoforms causes severe, early-onset deafness, deletion of TR beta 1 or TR beta 2 individually caused no obvious hearing loss in juvenile mice. However, over subsequent months, TR beta 1 deficiency resulted in progressive loss of hearing and loss of hair cells. TR beta 1-deficient mice had minimal changes in serum thyroid hormone and thyrotropin levels, indicating that hormonal imbalances were unlikely to cause hearing loss. The results suggest mutually shared roles for TR beta 1 and TR beta 2 in cochlear development and an unexpected requirement for TR beta 1 in the maintenance of hearing in adulthood.