Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model
- Autores
- Carignano, Camila; Barila, Esteban Pablo; Rias, Ezequiel Ignacio; Dionisio, Leonardo Raul; Aztiria, Eugenio Manuel; Spitzmaul, Guillermo Federico
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- DFNA2 is a progressive deafness caused by mutations in thevoltage-activated potassium channel KCNQ4. Hearing loss developswith age from a mild increase in hearing threshold to profounddeafness. The first phase starts around 10-15 years old, progressingto the last phase by the age of 70. Studies using transgenic mice forKcnq4 expressed in a mixed background demonstrated the implicationof outer hair cells (OHCs) at the initial phase. However, itcould not explain the last phase mechanisms of the disease. Geneticbackgrounds are known to influence disease expressivity. Tounmask the cause of profound deafness phenotype, we backcrossedKcnq4 knock-out allele to the inbred strain C3H/HeJ and investigatedinner and outer hair cell and spiral ganglion neuron (SGN)degeneration across lifespan. In addition to the already reportedOHC death, C3H/HeJ strain also exhibited inner hair cell (IHC) andSGN death. We tracked the spatiotemporal survival of cochlear cellsby plotting cytocochleograms and neuronal counts at different ages.Cell loss progressed from basal to apical turns with age for both haircells. Interestingly, the time-course of cell degeneration wasdifferent for each cell-type. While for OHCs it was already presentby week 3, IHC and neuronal loss started 30 weeks later. Weestablished that OHC loss kinetics slowed down from basal to apicalregions correlating with KCNQ4 expression pattern determined inwild-type mice. Our findings indicate that KCNQ4 plays differentialroles in each cochlear cell-type impacting in their survival ability.IHC and SGN neuron death generates severe hearing loss that couldbe associated to the last phase of DFNA2.
Fil: Carignano, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Barila, Esteban Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rias, Ezequiel Ignacio. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Aztiria, Eugenio Manuel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
The International Society for Neurochemistry and the American Society for Neurochemistry Meeting
Montreal
Canadá
International Society for Neurochemistry
American Society for Neurochemistry - Materia
-
KCNQ4
DEAFNESS
HAIR CELL
DEGENERATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/136814
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Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse modelCarignano, CamilaBarila, Esteban PabloRias, Ezequiel IgnacioDionisio, Leonardo RaulAztiria, Eugenio ManuelSpitzmaul, Guillermo FedericoKCNQ4DEAFNESSHAIR CELLDEGENERATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1DFNA2 is a progressive deafness caused by mutations in thevoltage-activated potassium channel KCNQ4. Hearing loss developswith age from a mild increase in hearing threshold to profounddeafness. The first phase starts around 10-15 years old, progressingto the last phase by the age of 70. Studies using transgenic mice forKcnq4 expressed in a mixed background demonstrated the implicationof outer hair cells (OHCs) at the initial phase. However, itcould not explain the last phase mechanisms of the disease. Geneticbackgrounds are known to influence disease expressivity. Tounmask the cause of profound deafness phenotype, we backcrossedKcnq4 knock-out allele to the inbred strain C3H/HeJ and investigatedinner and outer hair cell and spiral ganglion neuron (SGN)degeneration across lifespan. In addition to the already reportedOHC death, C3H/HeJ strain also exhibited inner hair cell (IHC) andSGN death. We tracked the spatiotemporal survival of cochlear cellsby plotting cytocochleograms and neuronal counts at different ages.Cell loss progressed from basal to apical turns with age for both haircells. Interestingly, the time-course of cell degeneration wasdifferent for each cell-type. While for OHCs it was already presentby week 3, IHC and neuronal loss started 30 weeks later. Weestablished that OHC loss kinetics slowed down from basal to apicalregions correlating with KCNQ4 expression pattern determined inwild-type mice. Our findings indicate that KCNQ4 plays differentialroles in each cochlear cell-type impacting in their survival ability.IHC and SGN neuron death generates severe hearing loss that couldbe associated to the last phase of DFNA2.Fil: Carignano, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Barila, Esteban Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Rias, Ezequiel Ignacio. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Aztiria, Eugenio Manuel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaThe International Society for Neurochemistry and the American Society for Neurochemistry MeetingMontrealCanadáInternational Society for NeurochemistryAmerican Society for NeurochemistryWiley2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/136814Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model; The International Society for Neurochemistry and the American Society for Neurochemistry Meeting; Montreal; Canadá; 2019; 159-1591471-4159CONICET DigitalCONICETenghttps://ri.conicet.gov.ar/handle/11336/99027info:eu-repo/semantics/altIdentifier/url/http://www.isnplaza.org/isn/program_and_abstractbook/ISN2019/PDF-Versions/ISN-ASN%202019%20Abstract%20Supplement.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:59Zoai:ri.conicet.gov.ar:11336/136814instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:58:59.743CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| title |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| spellingShingle |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model Carignano, Camila KCNQ4 DEAFNESS HAIR CELL DEGENERATION |
| title_short |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| title_full |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| title_fullStr |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| title_full_unstemmed |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| title_sort |
Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model |
| dc.creator.none.fl_str_mv |
Carignano, Camila Barila, Esteban Pablo Rias, Ezequiel Ignacio Dionisio, Leonardo Raul Aztiria, Eugenio Manuel Spitzmaul, Guillermo Federico |
| author |
Carignano, Camila |
| author_facet |
Carignano, Camila Barila, Esteban Pablo Rias, Ezequiel Ignacio Dionisio, Leonardo Raul Aztiria, Eugenio Manuel Spitzmaul, Guillermo Federico |
| author_role |
author |
| author2 |
Barila, Esteban Pablo Rias, Ezequiel Ignacio Dionisio, Leonardo Raul Aztiria, Eugenio Manuel Spitzmaul, Guillermo Federico |
| author2_role |
author author author author author |
| dc.subject.none.fl_str_mv |
KCNQ4 DEAFNESS HAIR CELL DEGENERATION |
| topic |
KCNQ4 DEAFNESS HAIR CELL DEGENERATION |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
DFNA2 is a progressive deafness caused by mutations in thevoltage-activated potassium channel KCNQ4. Hearing loss developswith age from a mild increase in hearing threshold to profounddeafness. The first phase starts around 10-15 years old, progressingto the last phase by the age of 70. Studies using transgenic mice forKcnq4 expressed in a mixed background demonstrated the implicationof outer hair cells (OHCs) at the initial phase. However, itcould not explain the last phase mechanisms of the disease. Geneticbackgrounds are known to influence disease expressivity. Tounmask the cause of profound deafness phenotype, we backcrossedKcnq4 knock-out allele to the inbred strain C3H/HeJ and investigatedinner and outer hair cell and spiral ganglion neuron (SGN)degeneration across lifespan. In addition to the already reportedOHC death, C3H/HeJ strain also exhibited inner hair cell (IHC) andSGN death. We tracked the spatiotemporal survival of cochlear cellsby plotting cytocochleograms and neuronal counts at different ages.Cell loss progressed from basal to apical turns with age for both haircells. Interestingly, the time-course of cell degeneration wasdifferent for each cell-type. While for OHCs it was already presentby week 3, IHC and neuronal loss started 30 weeks later. Weestablished that OHC loss kinetics slowed down from basal to apicalregions correlating with KCNQ4 expression pattern determined inwild-type mice. Our findings indicate that KCNQ4 plays differentialroles in each cochlear cell-type impacting in their survival ability.IHC and SGN neuron death generates severe hearing loss that couldbe associated to the last phase of DFNA2. Fil: Carignano, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina Fil: Barila, Esteban Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina Fil: Rias, Ezequiel Ignacio. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Aztiria, Eugenio Manuel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina The International Society for Neurochemistry and the American Society for Neurochemistry Meeting Montreal Canadá International Society for Neurochemistry American Society for Neurochemistry |
| description |
DFNA2 is a progressive deafness caused by mutations in thevoltage-activated potassium channel KCNQ4. Hearing loss developswith age from a mild increase in hearing threshold to profounddeafness. The first phase starts around 10-15 years old, progressingto the last phase by the age of 70. Studies using transgenic mice forKcnq4 expressed in a mixed background demonstrated the implicationof outer hair cells (OHCs) at the initial phase. However, itcould not explain the last phase mechanisms of the disease. Geneticbackgrounds are known to influence disease expressivity. Tounmask the cause of profound deafness phenotype, we backcrossedKcnq4 knock-out allele to the inbred strain C3H/HeJ and investigatedinner and outer hair cell and spiral ganglion neuron (SGN)degeneration across lifespan. In addition to the already reportedOHC death, C3H/HeJ strain also exhibited inner hair cell (IHC) andSGN death. We tracked the spatiotemporal survival of cochlear cellsby plotting cytocochleograms and neuronal counts at different ages.Cell loss progressed from basal to apical turns with age for both haircells. Interestingly, the time-course of cell degeneration wasdifferent for each cell-type. While for OHCs it was already presentby week 3, IHC and neuronal loss started 30 weeks later. Weestablished that OHC loss kinetics slowed down from basal to apicalregions correlating with KCNQ4 expression pattern determined inwild-type mice. Our findings indicate that KCNQ4 plays differentialroles in each cochlear cell-type impacting in their survival ability.IHC and SGN neuron death generates severe hearing loss that couldbe associated to the last phase of DFNA2. |
| publishDate |
2019 |
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2019 |
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http://hdl.handle.net/11336/136814 Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model; The International Society for Neurochemistry and the American Society for Neurochemistry Meeting; Montreal; Canadá; 2019; 159-159 1471-4159 CONICET Digital CONICET |
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Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model; The International Society for Neurochemistry and the American Society for Neurochemistry Meeting; Montreal; Canadá; 2019; 159-159 1471-4159 CONICET Digital CONICET |
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eng |
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eng |
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