GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice.
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.
van Looij
M A J
MA
Department of ENT, Erasmus Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands. m.vanlooij@erasmusmc.nl
van der Burg
H
H
van der Giessen
R S
RS
de Ruiter
M M
MM
van der Wees
J
J
van Doorninck
J H
JH
De Zeeuw
C I
CI
van Zanten
G A
GA
D000367:Age Factors; D000818:Animals; D003055:Cochlear Microphonic Potentials / Q000235:genetics*; D003056:Cochlear Nerve / Q000503:physiopathology; D003593:Cytoplasm / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000235:genetics; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005838:Genotype; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007011:Hypoparathyroidism / Q000150:complications / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D021782:Multicystic Dysplastic Kidney / Q000150:complications / Q000235:genetics; D013136:Spiral Ganglion / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse