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

نویسندگان

  • 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
چکیده

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.

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منابع مشابه

Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice

Calcium and integrin-binding protein 2 (CIB2) belongs to a protein family with four known members, CIB1 through CIB4, which are characterized by multiple calcium-binding EF-hand domains. Among the family members, the Cib1 and Cib2 genes are expressed in mouse cochlear hair cells, and mutations in the human CIB2 gene have been associated with nonsyndromic deafness DFNB48 and syndromic deafness U...

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Mutations in CIB2 calcium and integrin-binding protein disrupt auditory hair cell calcium homeostasis in Usher syndrome type 1J and non-syndromic deafness DFNB48.

1. Millan JM et al. An update on the genetics of usher syndrome. J Ophthalmol 2011: 2011: 417217. 2. Fettiplace R, Hackney CM. The sensory and motor roles of auditory hair cells. Nat Rev Neurosci 2006: 7: 19–29. 3. Riazuddin S. 2012. Alterations of the CIB2 calciumand integrinbinding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48 Nature Genetics. 2012: 44(11): 1265–1271.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2017