Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder.
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.
van der Wees
Jacqueline
J
Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
van Looij
Marjolein A J
MA
de Ruiter
M Martijn
MM
Elias
Helineth
H
van der Burg
Hans
H
Liem
Su-San
SS
Kurek
Dorota
D
Engel
J Doug
JD
Karis
Alar
A
van Zanten
Bert G A
BG
de Zeeuw
Chris I
CI
Grosveld
Frank G
FG
van Doorninck
J Hikke
JH
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*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators