title: Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder.
abstract: Patients with HDR syndrome suffer from hypoparathyroidism, deafness, and renal dysplasia due to a heterozygous deletion of the transcription factor GATA3. Since GATA3 is prominently expressed in both the inner ear and different parts of the auditory nervous system, it is not clear whether the deafness in HDR patients is caused by peripheral and/or central deficits. Therefore, we have created and examined heterozygous Gata3 knockout mice. Auditory brainstem response (ABR) thresholds of alert heterozygous Gata3 mice, analyzed from 1 to 19 months of age, showed a hearing loss of 30 dB compared to wild-type littermates. Neither physiological nor morphological abnormalities were found in the brainstem, cerebral cortex, the outer or the middle ear. In contrast, cochleae of heterozygous Gata3 mice showed significant progressive morphological degeneration starting with the outer hair cells (OHCs) at the apex and ultimately affecting all hair cells and supporting cells in the entire cochlea. Together, these findings indicate that hearing loss following Gata3 haploinsufficiency is peripheral in origin and that this defect is detectable from early postnatal development and maintains through adulthood.
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van der Wees
authors.forename: Marjolein A J
authors.initials: MA
authors.lastname: van Looij
authors.forename: M Martijn
authors.initials: MM
authors.lastname: de Ruiter
authors.forename: Helineth
authors.initials: H
authors.lastname: Elias
authors.forename: Hans
authors.initials: H
authors.lastname: van der Burg
authors.forename: Su-San
authors.initials: SS
authors.lastname: Liem
authors.forename: Dorota
authors.initials: D
authors.lastname: Kurek
authors.forename: J Doug
authors.initials: JD
authors.lastname: Engel
authors.forename: Alar
authors.initials: A
authors.lastname: Karis
authors.forename: Bert G A
authors.initials: BG
authors.lastname: van Zanten
authors.forename: Chris I
authors.initials: CI
authors.lastname: de Zeeuw
authors.forename: Frank G
authors.initials: FG
authors.lastname: Grosveld
authors.forename: J Hikke
authors.initials: JH
authors.lastname: van Doorninck
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D015834:Cochlear Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D050990:GATA3 Transcription Factor; D006239:Haplotypes / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators