CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival.

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 nonsyndromic profound hearing loss, with no evidence of vestibular or retinal dysfunction. Also, the generated CIB2-/- mice display an early onset profound deafness and have normal balance and retinal 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-/- 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-/- mice and CIB2 patients, unlike in Usher syndrome, of isolated hearing loss without balance and vision deficits.

• Authors: Vincent Michel, Kevin T Booth, Pranav Patni, Matteo Cortese, Hela Azaiez, Amel Bahloul, Kimia Kahrizi, Ménélik Labbé, Alice Emptoz, Andrea Lelli, Julie Dégardin, Typhaine Dupont, Asadollah Aghaie, Danuta Oficjalska-Pham, Serge Picaud, Hossein Najmabadi, Richard J Smith, Michael R Bowl, Steven Dm Brown, Paul Avan, Christine Petit, Aziz El-Amraoui
• Journal: EMBO molecular medicine (EMBO Mol Med) Vol. 9 Issue 12 Pg. 1711-1731 (12 2017) ISSN: 1757-4684 [Electronic] England
• PMID: 29084757 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Institut Pasteur. Published under the terms of the CC BY 4.0 license.

Chemical References

• Calcium-Binding Proteins
• Cib2 protein, mouse
• Membrane Proteins
• Whrn protein, mouse

Topics

• Animals
• Auditory Threshold
• Behavior, Animal
• Calcium-Binding Proteins (deficiency, genetics)
• Cell Survival
• Deafness (diagnosis, genetics)
• Disease Models, Animal
• Eye (diagnostic imaging, pathology)
• Female
• Hair Cells, Auditory, Inner (metabolism, pathology)
• Humans
• Male
• Maze Learning
• Mechanotransduction, Cellular (physiology)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pedigree
• Polymorphism, Single Nucleotide
• Retina (pathology, physiology)