title: Orphan glutamate receptor delta1 subunit required for high-frequency hearing.
abstract: The function of the orphan glutamate receptor delta subunits (GluRdelta1 and GluRdelta2) remains unclear. GluRdelta2 is expressed exclusively in the Purkinje cells of the cerebellum, and GluRdelta1 is prominently expressed in inner ear hair cells and neurons of the hippocampus. We found that mice lacking the GluRdelta1 protein displayed significant cochlear threshold shifts for frequencies of >16 kHz. These deficits correlated with a substantial loss of type IV spiral ligament fibrocytes and a significant reduction of endolymphatic potential in high-frequency cochlear regions. Vulnerability to acoustic injury was significantly enhanced; however, the efferent innervation of hair cells and the classic efferent inhibition of outer hair cells were unaffected. Hippocampal and vestibular morphology and function were normal. Our findings show that the orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea, and the locus encoding GluRdelta1 represents a candidate gene for congenital or acquired high-frequency hearing loss in humans.
authors: Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Jiangang
authors: J
authors: Gao
authors: Stéphane F
authors: SF
authors: Maison
authors: Xudong
authors: X
authors: Wu
authors: Keiko
authors: K
authors: Hirose
authors: Sherri M
authors: SM
authors: Jones
authors: Ildar
authors: I
authors: Bayazitov
authors: Yong
authors: Y
authors: Tian
authors: Guy
authors: G
authors: Mittleman
authors: Douglas B
authors: DB
authors: Matthews
authors: Stanislav S
authors: SS
authors: Zakharenko
authors: M Charles
authors: MC
authors: Liberman
authors: Jian
authors: J
authors: Zuo
mesh_terms: D000483:Alleles; D000818:Animals; D003051:Cochlea / Q000166:cytology / Q000473:pathology / Q000502:physiology; D004594:Electrophysiology; D017353:Gene Deletion; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000502:physiology; D006309:Hearing; D006579:Heterozygote; D006624:Hippocampus / Q000166:cytology; D006720:Homozygote; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*
chemical_list: D017470:Receptors, Glutamate; C108929:glutamate receptor delta 1