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Orphan glutamate receptor delta1 subunit required for high-frequency hearing.

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.

Pubmed ID: 17438141

Authors

  • Gao J
  • Maison SF
  • Wu X
  • Hirose K
  • Jones SM
  • Bayazitov I
  • Tian Y
  • Mittleman G
  • Matthews DB
  • Zakharenko SS
  • Liberman MC
  • Zuo J

Journal

Molecular and cellular biology

Publication Data

June 28, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: CA21765
  • Agency: NIDCD NIH HHS, Id: DC0188
  • Agency: NIDCD NIH HHS, Id: DC04477
  • Agency: NIDCD NIH HHS, Id: DC04761
  • Agency: NIDCD NIH HHS, Id: DC05168
  • Agency: NIDCD NIH HHS, Id: DC05761
  • Agency: NIDCD NIH HHS, Id: DC06471
  • Agency: NIDCD NIH HHS, Id: P30 DC005209
  • Agency: NIDCD NIH HHS, Id: P30 DC05209
  • Agency: NIDCD NIH HHS, Id: R01 DC000188
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-24
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-25
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-26
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-27
  • Agency: NIDCD NIH HHS, Id: R01 DC006443
  • Agency: NIDCD NIH HHS, Id: R01 DC006443-02

Mesh Terms

  • Alleles
  • Animals
  • Cochlea
  • Electrophysiology
  • Gene Deletion
  • Hair Cells, Auditory, Inner
  • Hearing
  • Heterozygote
  • Hippocampus
  • Homozygote
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • Neurons
  • Receptors, Glutamate