title: A study of whirlin isoforms in the mouse vestibular system suggests potential vestibular dysfunction in DFNB31-deficient patients.
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 (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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA, Department of Neurobiology and Anatomy, University of Utah, 20 North 1900 East, Salt Lake City, UT 84132, USA.
authors.forename: Pranav Dinesh
authors.initials: PD
authors.lastname: Mathur
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 304 Barkley Memorial Center, Lincoln, NE 68583, USA and.
authors.forename: Sarath
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
authors.forename: Deepti
authors.initials: D
authors.lastname: Vashist
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 304 Barkley Memorial Center, Lincoln, NE 68583, USA and.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 304 Barkley Memorial Center, Lincoln, NE 68583, USA and.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Jones
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA, Department of Neurobiology and Anatomy, University of Utah, 20 North 1900 East, Salt Lake City, UT 84132, USA, Division of Otolaryngology, Department of Surgery, University of Utah, 50 North Medical Drive, Salt Lake City, UT 84132, USA jun.yang@hsc.utah.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology / Q000503:physiopathology*; D006198:Hair Cells, Auditory / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D004856:Postural Balance; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; C477219:WHRN protein, human; C477218:Whrn protein, mouse