Cargando…
Grxcr2 is required for stereocilia morphogenesis in the cochlea
Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dime...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114524/ https://www.ncbi.nlm.nih.gov/pubmed/30157177 http://dx.doi.org/10.1371/journal.pone.0201713 |
_version_ | 1783351209625649152 |
---|---|
author | Avenarius, Matthew R. Jung, Jae-Yun Askew, Charles Jones, Sherri M. Hunker, Kristina L. Azaiez, Hela Rehman, Atteeq U. Schraders, Margit Najmabadi, Hossein Kremer, Hannie Smith, Richard J. H. Géléoc, Gwenaëlle S. G. Dolan, David F. Raphael, Yehoash Kohrman, David C. |
author_facet | Avenarius, Matthew R. Jung, Jae-Yun Askew, Charles Jones, Sherri M. Hunker, Kristina L. Azaiez, Hela Rehman, Atteeq U. Schraders, Margit Najmabadi, Hossein Kremer, Hannie Smith, Richard J. H. Géléoc, Gwenaëlle S. G. Dolan, David F. Raphael, Yehoash Kohrman, David C. |
author_sort | Avenarius, Matthew R. |
collection | PubMed |
description | Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity. |
format | Online Article Text |
id | pubmed-6114524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61145242018-09-17 Grxcr2 is required for stereocilia morphogenesis in the cochlea Avenarius, Matthew R. Jung, Jae-Yun Askew, Charles Jones, Sherri M. Hunker, Kristina L. Azaiez, Hela Rehman, Atteeq U. Schraders, Margit Najmabadi, Hossein Kremer, Hannie Smith, Richard J. H. Géléoc, Gwenaëlle S. G. Dolan, David F. Raphael, Yehoash Kohrman, David C. PLoS One Research Article Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity. Public Library of Science 2018-08-29 /pmc/articles/PMC6114524/ /pubmed/30157177 http://dx.doi.org/10.1371/journal.pone.0201713 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Avenarius, Matthew R. Jung, Jae-Yun Askew, Charles Jones, Sherri M. Hunker, Kristina L. Azaiez, Hela Rehman, Atteeq U. Schraders, Margit Najmabadi, Hossein Kremer, Hannie Smith, Richard J. H. Géléoc, Gwenaëlle S. G. Dolan, David F. Raphael, Yehoash Kohrman, David C. Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title | Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title_full | Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title_fullStr | Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title_full_unstemmed | Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title_short | Grxcr2 is required for stereocilia morphogenesis in the cochlea |
title_sort | grxcr2 is required for stereocilia morphogenesis in the cochlea |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114524/ https://www.ncbi.nlm.nih.gov/pubmed/30157177 http://dx.doi.org/10.1371/journal.pone.0201713 |
work_keys_str_mv | AT avenariusmatthewr grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT jungjaeyun grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT askewcharles grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT jonessherrim grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT hunkerkristinal grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT azaiezhela grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT rehmanatteequ grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT schradersmargit grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT najmabadihossein grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT kremerhannie grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT smithrichardjh grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT geleocgwenaellesg grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT dolandavidf grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT raphaelyehoash grxcr2isrequiredforstereociliamorphogenesisinthecochlea AT kohrmandavidc grxcr2isrequiredforstereociliamorphogenesisinthecochlea |