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

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. A lack of any of the first five USH1 proteins in mice leads to structural hair bundle defects in the embryo, causing congenital profound deafness, and balance dysfunction. The lack of CIB2 both in mice and humans, however, reveals that CIB2 is critical for hearing but not for balance and vision.
Source: EMBO Molecular Medicine - Category: Molecular Biology Authors: Tags: Research Article Source Type: research