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EMBO Mol Med. 2017 Dec;9(12):1711-1731. doi: 10.15252/emmm.201708087.

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

Author information

1
Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France.
2
Unité Mixte de Recherche- UMRS 1120, Institut National de la Santé et de la Recherche Médicale, Paris, France.
3
Sorbonne Universités, UPMC Univ Paris06, Paris, France.
4
Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology- Head and Neck Surgery, University of Iowa, Iowa City, Iowa.
5
Department of Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
6
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
7
Retinal information processing - Pharmacology and Pathology, Institut de la Vision, Paris, France.
8
Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, Paris, France.
9
Mammalian Genetics Unit, MRC Harwell Institute, Oxford, UK.
10
Laboratoire de Biophysique Sensorielle, Faculté de Médecine, Biophysique Médicale, Centre Jean Perrin, Université d'Auvergne, Clermont-Ferrand, France.
11
Collège de France, Paris, France.
12
Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France aziz.el-amraoui@pasteur.fr.

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.

KEYWORDS:

CIB proteins; Usher syndrome diagnosis; human and mouse deafness

PMID:
29084757
PMCID:
PMC5709726
DOI:
10.15252/emmm.201708087
[Indexed for MEDLINE]
Free PMC Article

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