TY - JOUR
T1 - Age-related hearing loss and degeneration of cochlear hair cells in mice lacking thyroid hormone receptor β1
AU - Ng, Lily
AU - Cordas, Emily
AU - Wu, Xuefeng
AU - Vella, Kristen R.
AU - Hollenberg, Anthony N.
AU - Forrest, Douglas
N1 - Publisher Copyright:
© 2015 by the Endocrine Society.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - A key function of the thyroid hormone receptor β (Thrb) gene is in the development of auditory function. However, the roles of the 2 receptor isoforms, TRβ1 and TRβ2, 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 TRβ1 in mice with a Thrbb1 reporter allele that expresses β-galactosidase instead of TRβ1. In the immature cochlea, β-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 TRβ isoforms causes severe, early-onset deafness, deletion of TRβ1 or TRβ2 individually caused no obvious hearing loss in juvenile mice. However, over subsequent months, TRβ1 deficiency resulted in progressive loss of hearing and loss of hair cells. TRβ1-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 TRβ1 and TRβ2 in cochlear development and an unexpected requirement for TRβ1 in the maintenance of hearing in adulthood.
AB - A key function of the thyroid hormone receptor β (Thrb) gene is in the development of auditory function. However, the roles of the 2 receptor isoforms, TRβ1 and TRβ2, 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 TRβ1 in mice with a Thrbb1 reporter allele that expresses β-galactosidase instead of TRβ1. In the immature cochlea, β-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 TRβ isoforms causes severe, early-onset deafness, deletion of TRβ1 or TRβ2 individually caused no obvious hearing loss in juvenile mice. However, over subsequent months, TRβ1 deficiency resulted in progressive loss of hearing and loss of hair cells. TRβ1-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 TRβ1 and TRβ2 in cochlear development and an unexpected requirement for TRβ1 in the maintenance of hearing in adulthood.
UR - http://www.scopus.com/inward/record.url?scp=84943596667&partnerID=8YFLogxK
U2 - 10.1210/en.2015-1468
DO - 10.1210/en.2015-1468
M3 - Article
C2 - 26241124
AN - SCOPUS:84943596667
SN - 0013-7227
VL - 156
SP - 3853
EP - 3865
JO - Endocrinology
JF - Endocrinology
IS - 10
ER -