IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v2y2011i1d10.1038_ncomms1200.html
   My bibliography  Save this article

Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human

Author

Listed:
  • Nikoletta Charizopoulou

    (Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

  • Andrea Lelli

    (University of Virginia School of Medicine)

  • Margit Schraders

    (Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
    Nijmegen Centre of Molecular Life Sciences, Radboud University Nijmegen)

  • Kausik Ray

    (Section on Signal Transduction, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

  • Michael S. Hildebrand

    (University of Iowa)

  • Arabandi Ramesh

    (University of Madras)

  • C. R. Srikumari Srisailapathy

    (University of Madras)

  • Jaap Oostrik

    (Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
    Nijmegen Centre of Molecular Life Sciences, Radboud University Nijmegen)

  • Ronald J. C. Admiraal

    (Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre)

  • Harold R. Neely

    (Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

  • Joseph R. Latoche

    (Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

  • Richard J. H. Smith

    (University of Iowa)

  • John K. Northup

    (Section on Signal Transduction, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

  • Hannie Kremer

    (Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
    Nijmegen Centre of Molecular Life Sciences, Radboud University Nijmegen)

  • Jeffrey R. Holt

    (University of Virginia School of Medicine)

  • Konrad Noben-Trauth

    (Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health)

Abstract

Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion. A missense mutation in the PDZ domain has an attenuating effect on mechanotransduction and the acquisition of mature inner hair cell potassium currents. Magnitude and temporal progression of wave I amplitude of afferent neurons correlate with susceptibility and resistance to audiogenic seizures. The Gipc3343A allele disrupts the structure of the stereocilia bundle and affects long-term function of auditory hair cells and spiral ganglion neurons. Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells.

Suggested Citation

  • Nikoletta Charizopoulou & Andrea Lelli & Margit Schraders & Kausik Ray & Michael S. Hildebrand & Arabandi Ramesh & C. R. Srikumari Srisailapathy & Jaap Oostrik & Ronald J. C. Admiraal & Harold R. Neel, 2011. "Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human," Nature Communications, Nature, vol. 2(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1200
    DOI: 10.1038/ncomms1200
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms1200
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms1200?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1200. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.