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

Vincent Michel (1) , Kevin T Booth (2) , Pranav Patni (1) , Matteo Cortese (1) , Hela Azaiez (2) , Amel Bahloul (1) , Kimia Kahrizi (3) , Ménélik Labbe (1) , Alice Emptoz (1) , Andrea Lelli (1) , Julie Dégardin (4) , Typhaine Dupont (1) , Asadollah Aghaie (1, 4) , Danuta Oficjalska‐pham (1) , Serge Picaud (4) , Hossein Najmabadi (3) , Richard J Smith (2) , Michael R Bowl (5) , Steven Dm Brown (5) , Paul Avan (6) , Christine Petit (1) , Aziz El‐amraoui (1)

1 Génétique et Physiologie de l'Audition
2 University of Iowa [Iowa City]
3 University of Social Welfare and Rehabilitation Sciences [Tehran]
4 Institut de la Vision
5 MRC Harwell
6 Laboratoire de Biophysique sensorielle

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.

Mots clés: CIB proteins; human and mouse deafness; Usher syndrome diagnosis Subject Categories Genetics; Gene Therapy & Genetic Disease; Neuroscience

Domaines: Sciences du Vivant [q-bio]; Organes des sens

Vincent Michel, Kevin T Booth, Pranav Patni, Matteo Cortese, Hela Azaiez, et al.. CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival. EMBO Molecular Medicine, 2017, 9 (12), pp.1711 - 1731. ⟨10.15252/emmm.201708087⟩. ⟨hal-01661175⟩