Neurobiology of Disease (Jun 2004)
Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder
- Jacqueline van der Wees,
- Marjolein A.J van Looij,
- M.Martijn de Ruiter,
- Helineth Elias,
- Hans van der Burg,
- Su-San Liem,
- Dorota Kurek,
- J.Doug Engel,
- Alar Karis,
- Bert G.A van Zanten,
- Chris I De Zeeuw,
- Frank G Grosveld,
- J.Hikke van Doorninck
Affiliations
- Jacqueline van der Wees
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Marjolein A.J van Looij
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- M.Martijn de Ruiter
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Helineth Elias
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Hans van der Burg
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Su-San Liem
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Dorota Kurek
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- J.Doug Engel
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Alar Karis
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Bert G.A van Zanten
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Chris I De Zeeuw
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Frank G Grosveld
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- J.Hikke van Doorninck
- Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of ENT, Erasmus Medical Center, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Biochemistry, Molecular Biology and Cell Biology, North Western University, Evanston, IL 60208, USA; Department of Integrative Zoology, University of Tartu, Tartu 51014, Estonia
- Journal volume & issue
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Vol. 16,
no. 1
pp. 169 – 178
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.
