GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice

M.A.J. van Looij; H. van der Burg; R.S. van der Giessen; M.M. de Ruiter; J. van der Wees; J.H. van Doorninck; C.I. De Zeeuw; G.A. van Zanten

Neurobiology of Disease (Dec 2005)

GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice

M.A.J. van Looij,
H. van der Burg,
R.S. van der Giessen,
M.M. de Ruiter,
J. van der Wees,
J.H. van Doorninck,
C.I. De Zeeuw,
G.A. van Zanten

Affiliations

M.A.J. van Looij: Department of ENT, Erasmus Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands; Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Corresponding author. Department of Otorhinolaryngology, Erasmus MC, PO Box 2060, 3000 CB Rotterdam, The Netherlands. Fax: +31 10 4635660.
H. van der Burg: Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
R.S. van der Giessen: Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
M.M. de Ruiter: Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
J. van der Wees: Department of Cell Biology and Genetics, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands
J.H. van Doorninck: Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
C.I. De Zeeuw: Department of Neuroscience, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
G.A. van Zanten: Department of ENT, Erasmus Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands; Department of ENT/Audiology, F.02.504, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

Journal volume & issue: Vol. 20, no. 3
pp. 890 – 897

Abstract

Read online

Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing loss due to GATA3 haploinsufficiency has been shown to be peripheral in origin, but it is unclear to what extent potential aberrations in the outer hair cells (OHCs) contribute to this disorder. To further elucidate the pathophysiological mechanism underlying the hearing defect in HDR-syndrome, we investigated the OHCs in heterozygous Gata3-knockout mice at both the functional and morphological level. While the signal-to-noise ratios of distortion product otoacoustic emissions (DPOAE) in wild type mice did not change significantly during the first half-year of live, those in the heterozygous Gata3 mice decreased dramatically. In addition, both light microscopic and transmission electron microscopic analyses showed that the number of OHCs containing vacuoles was increased in the mutants. Together, these findings indicate that outer hair cell malfunctioning plays a major role in the hearing loss in HDR-syndrome.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords