title: Autonomous functions of murine thyroid hormone receptor TRα and TRβ in cochlear hair cells.
abstract: Thyroid hormone acts on gene transcription by binding to its nuclear receptors TRα1 and TRβ. Whereas global deletion of TRβ causes deafness, global TRα-deficient mice have normal hearing thresholds. Since the individual roles of the two receptors in cochlear hair cells are still unclear, we generated mice with a hair cell-specific mutation of TRα1 or deletion of TRβ using the Cre-loxP system. Hair cell-specific TRβ mutant mice showed normal hearing thresholds but delayed BK channel expression in inner hair cells, slightly stronger outer hair cell function, and slightly reduced amplitudes of auditory brainstem responses. In contrast, hair cell-specific TRα mutant mice showed normal timing of BK channel expression, slightly reduced outer hair cell function, and slightly enhanced amplitudes of auditory brainstem responses. Our data demonstrate that TRβ-related deafness originates outside of hair cells and that TRα and TRβ play opposing, non-redundant roles in hair cells. A role for thyroid hormone receptors in controlling key regulators that shape signal transduction during development is discussed. Thyroid hormone may act through different thyroid hormone receptor activities to permanently alter the sensitivity of auditory neurotransmission.
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Dettling
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Franz
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Sze Chim
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Molecular Genetics, THRC, Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bress
authors.affiliation: Department of Biophysics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Brandt
authors.affiliation: Department of Signal Transduction & Transgenic Models, Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.affiliation: Molecular Genetics, THRC, Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.affiliation: Department of Biophysics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.affiliation: Institut de Génomique Fonctionnelle, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany. Electronic address: marlies.knipper@uni-tuebingen.de.
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001307:Auditory Perception; D001933:Brain Stem / Q000378:metabolism; D005786:Gene Expression Regulation; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000502:physiology; D051656:KCNQ Potassium Channels / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000378:metabolism; D009928:Organ Specificity; D017084:Otoacoustic Emissions, Spontaneous; D010641:Phenotype; D011995:Recombination, Genetic / Q000235:genetics; D015398:Signal Transduction; D013680:Tectorial Membrane / Q000254:growth & development / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D051656:KCNQ Potassium Channels; C492167:Kcnq4 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta
keywords: ABR amplitudes; BK channel; Cochlear hair cells; Conditional mutant mice; Hypothyroidism; Thyroid hormone receptor α, β