title: Hair bundle defects and loss of function in the vestibular end organs of mice lacking the receptor-like inositol lipid phosphatase PTPRQ.
abstract: Recent studies have shown that mutations in PTPRQ, a gene encoding a receptor-like inositol lipid phosphatase, cause recessive, nonsyndromic, hereditary hearing loss with associated vestibular dysfunction. Although null mutations in Ptprq cause the loss of high-frequency auditory hair cells and deafness in mice, a loss of vestibular hair cells and overt behavioral defects characteristic of vestibular dysfunction have not been described. Hair bundle structure and vestibular function were therefore examined in Ptprq mutant mice. Between postnatal days 5 and 16, hair bundles in the extrastriolar regions of the utricle in Ptprq(-/-) mice become significantly longer than those in heterozygous controls. This increase in length (up to 50%) is accompanied by the loss and fusion of stereocilia. Loss and fusion of stereocilia also occurs in the striolar region of the utricle in Ptprq(-/-) mice, but is not accompanied by hair bundle elongation. These abnormalities persist until 12 months of age but are not accompanied by significant hair cell loss. Hair bundle defects are also observed in the saccule and ampullae of Ptprq(-/-) mice. At ∼3 months of age, vestibular evoked potentials were absent from the majority (12 of 15) of Ptprq(-/-) mice examined, and could only be detected at high stimulus levels in the other 3 mutants. Subtle but distinct defects in swimming behavior were detected in most (seven of eight) mutants tested. The results reveal a distinct phenotype in the vestibular system of Ptprq(-/-) mice and suggest similar hair bundle defects may underlie the vestibular dysfunction reported in humans with mutations in PTPRQ.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Goodyear
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.forename: Louise
authors.initials: L
authors.lastname: Sharifi
authors.forename: Andy
authors.initials: A
authors.lastname: Forge
authors.forename: Guy P
authors.initials: GP
authors.lastname: Richardson
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000473:pathology* / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D010590:Phalloidine / Q000378:metabolism; D011571:Psychoacoustics; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D059547:Stereocilia / Q000473:pathology / Q000648:ultrastructure; D015837:Vestibular Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D000199:Actins; D010590:Phalloidine; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D043562:Receptors, G-Protein-Coupled; C485949:Adgrv1 protein, mouse