title: Age-Related Hearing Loss and Degeneration of Cochlear Hair Cells in Mice Lacking Thyroid Hormone Receptor β1.
abstract: 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 Thrb(b1) 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.
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Lily
authors.initials: L
authors.lastname: Ng
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Emily
authors.initials: E
authors.lastname: Cordas
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Vella
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hollenberg
authors.affiliation: Laboratory of Endocrinology and Receptor Biology (L.N., E.C., X.W., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Division of Endocrinology, Diabetes and Metabolism (K.R.V., A.N.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Douglas
authors.initials: D
authors.lastname: Forrest
mesh_terms: D000375:Aging; D000818:Animals; D003051:Cochlea / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology; D034381:Hearing Loss / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009925:Organ of Corti / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D013972:Thyrotropin; D001616:beta-Galactosidase