Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder
| Autor: | Chris I. De Zeeuw, J. Hikke van Doorninck, Alar Karis, Frank Grosveld, J. Doug Engel, Martijn M. De Ruiter, Jacqueline van der Wees, Marjolein A.J. van Looij, Hans van der Burg, Helineth Elias, Bert G.A. van Zanten, Su San Liem, Dorota Kurek |
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| Přispěvatelé: | Cell biology, Neurosciences, Erasmus School of Health Policy & Management, Otorhinolaryngology and Head and Neck Surgery |
| Rok vydání: | 2004 |
| Předmět: |
Pathology
medicine.medical_specialty Hearing loss Cochlear Diseases HDR GATA3 Transcription Factor Biology Audiology Deafness lcsh:RC321-571 Mice GATA3 medicine otorhinolaryngologic diseases Animals Inner ear Hearing Loss lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cochlea Otic Mice Knockout Auditory Threshold DNA-Binding Proteins Mice Inbred C57BL Auditory brainstem response medicine.anatomical_structure Neurology Acoustic Stimulation Haplotypes Middle ear Trans-Activators Degeneration Hair cell sense organs medicine.symptom Haploinsufficiency |
| Zdroj: | Neurobiology of Disease, 16(1), 169-178. Academic Press Neurobiology of Disease, Vol 16, Iss 1, Pp 169-178 (2004) |
| ISSN: | 0969-9961 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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