Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.
The genes for alpha- and beta-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse alpha-tectorin gene was found to cause loss of cochlear sensitivity (). Here we describe that mRNA levels for beta-tectorin, but not alpha-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of beta-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (), can also lead to permanently reduced beta-tectorin protein levels in the tectorial membrane. beta-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low beta-tectorin levels in the tectorial membrane and suggest for the first time that beta-tectorin may be required for development of normal hearing.
Knipper
M
M
Department of Oto-Rhino-Laryngology, Tübingen Centre for Hearing Research, University of Tübingen, Röntgenweg 11, D-72076 Tübingen, Germany. Marlies.Knipper@uni-tuebingen.de
Richardson
G
G
Mack
A
A
Müller
M
M
Goodyear
R
R
Limberger
A
A
Rohbock
K
K
Köpschall
I
I
Zenner
H P
HP
Zimmermann
U
U
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism* / Q000648:ultrastructure; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D006309:Hearing / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000096:biosynthesis*; D008713:Methimazole / Q000494:pharmacology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000172:deficiency*; D014018:Tissue Distribution
D013956:Antithyroid Agents; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C093123:TECTB protein, human; D013963:Thyroid Hormones; D008713:Methimazole