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 (
Dfnb31(wi/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
Dfnb31(wi/wi) vestibular organs, while only C-whirlin is expressed in
Dfnb31(neo/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
Dfnb31(neo/neo) and
Dfnb31(wi/wi) mice. Swimming and rotarod tests demonstrate that the two
Dfnb31 mutants have balance problems, with
Dfnb31(wi/wi) mice being more affected than
Dfnb31(neo/neo) mice. Because
Dfnb31(wi/wi) and
Dfnb31(neo/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.