Journal article
CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival
EMBO molecular medicine, Vol.9(12), pp.1711-1731
12/01/2017
DOI: 10.15252/emmm.201708087
PMCID: PMC5709726
PMID: 29084757
Abstract
Defects of CIB2, calcium-and integrin-binding protein 2, have been reported to cause isolated deafness, DFNB48 and Usher syndrome type-IJ, characterized by congenital profound deafness, balance defects and blindness. We report here two new nonsense mutations (pGln12* and pTyr110*) in CIB2 patients displaying nonsyn-dromic profound hearing loss, with no evidence of vestibular or retinal dysfunction. Also, the generated CIB2 À/À mice display an early onset profound deafness and have normal balance and reti-nal functions. In these mice, the mechanoelectrical transduction currents are totally abolished in the auditory hair cells, whilst they remain unchanged in the vestibular hair cells. The hair bundle morphological abnormalities of CIB2 À/À mice, unlike those of mice defective for the other five known USH1 proteins, begin only after birth and lead to regression of the stereocilia and rapid hair-cell death. This essential role of CIB2 in mechanotransduction and cell survival that, we show, is restricted to the cochlea, probably accounts for the presence in CIB2 À/À mice and CIB2 patients, unlike in Usher syndrome, of isolated hearing loss without balance and vision deficits.
Details
- Title: Subtitle
- CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival
- Creators
- Vincent Michel - Génétique et Physiologie de l'AuditionKevin T Booth - University of Iowa [Iowa City]Pranav Patni - Génétique et Physiologie de l'AuditionMatteo Cortese - Génétique et Physiologie de l'AuditionHela Azaiez - University of Iowa [Iowa City]Amel Bahloul - Génétique et Physiologie de l'AuditionKimia Kahrizi - University of Social Welfare and Rehabilitation Sciences [Tehran]Ménélik Labbe - Génétique et Physiologie de l'AuditionAlice Emptoz - Génétique et Physiologie de l'AuditionAndrea Lelli - Génétique et Physiologie de l'AuditionJulie Dégardin - Institut de la VisionTyphaine Dupont - Génétique et Physiologie de l'AuditionAsadollah Aghaie - Université Pierre et Marie Curie - Paris 6Danuta Oficjalska‐Pham - Génétique et Physiologie de l'AuditionSerge Picaud - Institut de la VisionHossein Najmabadi - University of Social Welfare and Rehabilitation Sciences [Tehran]Richard J Smith - University of Iowa [Iowa City]Michael R Bowl - MRC HarwellSteven D. M Brown - MRC HarwellPaul Avan - Equipe Biophysique Neurosensorielle [Neuro-Dol]Christine Petit - Génétique et Physiologie de l'AuditionAziz El‐Amraoui - Génétique et Physiologie de l'Audition
- Resource Type
- Journal article
- Publication Details
- EMBO molecular medicine, Vol.9(12), pp.1711-1731
- DOI
- 10.15252/emmm.201708087
- PMID
- 29084757
- PMCID
- PMC5709726
- NLM abbreviation
- EMBO Mol Med
- ISSN
- 1757-4676
- eISSN
- 1757-4684
- Publisher
- Wiley Open Access
- Grant note
- DOI: 10.13039/501100000780, name: European Commission, award: ERC‐2011‐ADG_294570; DOI: 10.13039/501100004963, name: Seventh Framework Programme, award: HEALTH‐F2‐2010‐242013; DOI: 10.13039/100010661, name: Horizon 2020 Framework Programme, award: 665807; DOI: 10.13039/501100001665, name: Agence Nationale de la Recherche, award: ANR‐15‐RHUS‐0001, ANR‐10‐LABX‐65, ANR‐11‐IDEX‐0004‐02, ANR‐11‐BSV5‐0011; DOI: 10.13039/501100008393, name: Fondation BNP Paribas; DOI: 10.13039/501100000265, name: Medical Research Council, award: MC_U142684175; DOI: 10.13039/501100003968, name: Iran National Science Foundation, award: 95S47307; DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: DC003544, DC002842, DC012049
- Language
- English
- Date published
- 12/01/2017
- 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
- 9984006461902771
Metrics
57 Record Views