Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9

Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the...
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Gespeichert in:

Autor*in:	Ursula Stalmann [verfasserIn] Albert Justin Franke [verfasserIn] Hanan Al-Moyed [verfasserIn] Nicola Strenzke [verfasserIn] Ellen Reisinger [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	inner hair cells outer hair cells synapse maturation degeneration otoacoustic emissions hearing loss

Übergeordnetes Werk:	In: Frontiers in Cellular Neuroscience - Frontiers Media S.A., 2008, 15(2021)
Übergeordnetes Werk:	volume:15 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fncel.2021.677543

Katalog-ID:	DOAJ057207305

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520			\|a Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients.
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allfieldsGer	10.3389/fncel.2021.677543 doi (DE-627)DOAJ057207305 (DE-599)DOAJb7cc15a3a0094c49896df0a707d4e557 DE-627 ger DE-627 rakwb eng RC321-571 Ursula Stalmann verfasserin aut Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients. inner hair cells outer hair cells synapse maturation degeneration otoacoustic emissions hearing loss Neurosciences. Biological psychiatry. Neuropsychiatry Albert Justin Franke verfasserin aut Hanan Al-Moyed verfasserin aut Nicola Strenzke verfasserin aut Ellen Reisinger verfasserin aut Ellen Reisinger verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:15 year:2021 https://doi.org/10.3389/fncel.2021.677543 kostenfrei https://doaj.org/article/b7cc15a3a0094c49896df0a707d4e557 kostenfrei https://www.frontiersin.org/articles/10.3389/fncel.2021.677543/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021
allfieldsSound	10.3389/fncel.2021.677543 doi (DE-627)DOAJ057207305 (DE-599)DOAJb7cc15a3a0094c49896df0a707d4e557 DE-627 ger DE-627 rakwb eng RC321-571 Ursula Stalmann verfasserin aut Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients. inner hair cells outer hair cells synapse maturation degeneration otoacoustic emissions hearing loss Neurosciences. Biological psychiatry. Neuropsychiatry Albert Justin Franke verfasserin aut Hanan Al-Moyed verfasserin aut Nicola Strenzke verfasserin aut Ellen Reisinger verfasserin aut Ellen Reisinger verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:15 year:2021 https://doi.org/10.3389/fncel.2021.677543 kostenfrei https://doaj.org/article/b7cc15a3a0094c49896df0a707d4e557 kostenfrei https://www.frontiersin.org/articles/10.3389/fncel.2021.677543/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021
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callnumber-first	R - Medicine
author	Ursula Stalmann
spellingShingle	Ursula Stalmann misc RC321-571 misc inner hair cells misc outer hair cells misc synapse maturation misc degeneration misc otoacoustic emissions misc hearing loss misc Neurosciences. Biological psychiatry. Neuropsychiatry Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9
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topic_title	RC321-571 Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9 inner hair cells outer hair cells synapse maturation degeneration otoacoustic emissions hearing loss
topic	misc RC321-571 misc inner hair cells misc outer hair cells misc synapse maturation misc degeneration misc otoacoustic emissions misc hearing loss misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc inner hair cells misc outer hair cells misc synapse maturation misc degeneration misc otoacoustic emissions misc hearing loss misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9
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title_full	Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9
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title_sort	otoferlin is required for proper synapse maturation and for maintenance of inner and outer hair cells in mouse models for dfnb9
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title_auth	Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9
abstract	Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients.
abstractGer	Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients.
abstract_unstemmed	Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof–/–) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof–/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof–/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof–/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof–/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients.
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title_short	Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9
url	https://doi.org/10.3389/fncel.2021.677543 https://doaj.org/article/b7cc15a3a0094c49896df0a707d4e557 https://www.frontiersin.org/articles/10.3389/fncel.2021.677543/full https://doaj.org/toc/1662-5102
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Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9

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