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 o...

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Published inNeurobiology of disease Vol. 20; no. 3; pp. 890 - 897
Main Authors van Looij, M.A.J., van der Burg, H., van der Giessen, R.S., de Ruiter, M.M., van der Wees, J., van Doorninck, J.H., De Zeeuw, C.I., van Zanten, G.A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.12.2005
Elsevier
Subjects
Age Factors
Animals
Cochlear Microphonic Potentials - genetics
Cochlear Nerve - physiopathology
Cytoplasm - pathology
Cytoplasm - ultrastructure
Disease Models, Animal
DPOAE
Evoked Potentials, Auditory - genetics
Female
GATA3
GATA3 Transcription Factor - genetics
Genotype
Hair Cells, Auditory, Outer - metabolism
Hair Cells, Auditory, Outer - pathology
Hair Cells, Auditory, Outer - physiopathology
HDR-syndrome
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - pathology
Hearing Loss, Sensorineural - physiopathology
Hypoparathyroidism - complications
Hypoparathyroidism - genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron, Transmission
Multicystic Dysplastic Kidney - complications
Multicystic Dysplastic Kidney - genetics
OHC
Spiral Ganglion - physiopathology
Synaptic Transmission - genetics
Vacuole
Vacuoles - pathology
Vacuoles - ultrastructure
HDR-syndrome
DPOAE
IHC
EM
OHC
GATA3
Ht
Vacuole
Hearing loss
ABR
OAE
PC
NF
Wt
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Abstract 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.
AbstractList 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.
Author van Looij, M.A.J.
van Doorninck, J.H.
van der Burg, H.
De Zeeuw, C.I.
van der Giessen, R.S.
van der Wees, J.
van Zanten, G.A.
de Ruiter, M.M.
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Issue 3
Keywords HDR-syndrome
DPOAE
IHC
EM
OHC
GATA3
Ht
Vacuole
Hearing loss
ABR
OAE
PC
NF
Wt
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Snippet Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing...
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SubjectTerms Age Factors
Animals
Cochlear Microphonic Potentials - genetics
Cochlear Nerve - physiopathology
Cytoplasm - pathology
Cytoplasm - ultrastructure
Disease Models, Animal
DPOAE
Evoked Potentials, Auditory - genetics
Female
GATA3
GATA3 Transcription Factor - genetics
Genotype
Hair Cells, Auditory, Outer - metabolism
Hair Cells, Auditory, Outer - pathology
Hair Cells, Auditory, Outer - physiopathology
HDR-syndrome
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - pathology
Hearing Loss, Sensorineural - physiopathology
Hypoparathyroidism - complications
Hypoparathyroidism - genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron, Transmission
Multicystic Dysplastic Kidney - complications
Multicystic Dysplastic Kidney - genetics
OHC
Spiral Ganglion - physiopathology
Synaptic Transmission - genetics
Vacuole
Vacuoles - pathology
Vacuoles - ultrastructure
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Title GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice
URI https://dx.doi.org/10.1016/j.nbd.2005.05.025
https://www.ncbi.nlm.nih.gov/pubmed/15994092
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