Journal article
Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
Nature communications, Vol.2(1), 201
02/2011
DOI: 10.1038/ncomms1200
PMCID: PMC3105340
PMID: 21326233
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.
Details
- Title: Subtitle
- Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
- Creators
- Arabandi Ramesh - Department of Genetics, University of MadrasAndrea Lelli - Department of Neuroscience and Otolaryngology, University of Virginia School of MedicineRichard J. H Smith - Department of Otolaryngology, University of IowaMargit Schraders - Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen Centre of Molecular Life Sciences, Radboud University NijmegenJeffrey R Holt - Department of Neuroscience and Otolaryngology, University of Virginia School of MedicineC. R. Srikumari Srisailapathy - Department of Genetics, University of MadrasRonald J. C Admiraal - Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical CentreHarold R Neely - Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthHannie Kremer - Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen Centre of Molecular Life Sciences, Radboud University NijmegenJaap Oostrik - Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen Centre of Molecular Life Sciences, Radboud University NijmegenMichael S Hildebrand - Department of Otolaryngology, University of IowaJohn K Northup - Section on Signal Transduction, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthNikoletta Charizopoulou - Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthKausik Ray - Section on Signal Transduction, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthJoseph R Latoche - Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthKonrad Noben-Trauth - Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.2(1), 201
- DOI
- 10.1038/ncomms1200
- PMID
- 21326233
- PMCID
- PMC3105340
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Language
- English
- Date published
- 02/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006429902771
Metrics
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