A study of whirlin isoforms in the mouse vestibular system suggests potential vestibular dysfunction in DFNB31-deficient patients

Pranav Dinesh Mathur, Sarath Vijayakumar, Deepti Vashist, Sherri M. Jones, Timothy A. Jones, Jun Yang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The DFNB31 gene plays an indispensable role in the cochlea and retina. Mutations in this gene disrupt its various isoforms and lead to non-syndromic deafness, blindness and deaf-blindness. However, the known expression of Dfnb31, the mouse ortholog of DFNB31, in vestibular organs and the potential vestibular-deficient phenotype observed in one Dfnb31 mutant mouse (Dfnb31wi/wi) suggest that DFNB31 may also be important for vestibular function. In this study, we find that full-length (FL-) and C-terminal (C-) whirlin isoforms are expressed in the vestibular organs, where their stereociliary localizations are similar to those of developing cochlear inner hair cells. No whirlin is detected in Dfnb31wi/wi vestibular organs, while only C-whirlin is expressed in Dfnb31neo/neo vestibular organs. Both FL- and C-whirlin isoforms are required for normal vestibular stereociliary growth, although they may play slightly different roles in the central and peripheral zones of the crista ampullaris. Vestibular sensory-evoked potentials demonstrate severe to profound vestibular deficits in Dfnb31neo/neo and Dfnb31wi/wi mice. Swimming and rotarod tests demonstrate that the two Dfnb31 mutants have balance problems, with Dfnb31wi/wi mice being more affected than Dfnb31neo/neo mice. Because Dfnb31wi/wi and Dfnb31neo/neo mice faithfully recapitulate hearing and vision symptoms in patients, our findings of vestibular dysfunction in these Dfnb31 mutants raise the question of whether DFNB31-deficient patients may acquire vestibular as well as hearing and vision loss.

Original languageEnglish (US)
Pages (from-to)7017-7030
Number of pages14
JournalHuman Molecular Genetics
Volume24
Issue number24
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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