Hair bundle defects and loss of function in the vestibular end organs of mice lacking the receptor-like inositol lipid phosphatase PTPRQ

Richard J. Goodyear, Sherri M Jones, Louise Sharifi, Andy Forge, Guy P. Richardson

Research output: Contribution to journalArticle

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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 highfrequency 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.

Original languageEnglish (US)
Pages (from-to)2762-2772
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number8
DOIs
StatePublished - Feb 22 2012

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Lipids
Saccule and Utricle
Stereocilia
Mutation
Auditory Hair Cells
Vestibular Hair Cells
Alopecia
Deafness
myo-inositol-1 (or 4)-monophosphatase
Evoked Potentials
Phenotype
Genes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Hair bundle defects and loss of function in the vestibular end organs of mice lacking the receptor-like inositol lipid phosphatase PTPRQ. / Goodyear, Richard J.; Jones, Sherri M; Sharifi, Louise; Forge, Andy; Richardson, Guy P.

In: Journal of Neuroscience, Vol. 32, No. 8, 22.02.2012, p. 2762-2772.

Research output: Contribution to journalArticle

Goodyear, Richard J. ; Jones, Sherri M ; Sharifi, Louise ; Forge, Andy ; Richardson, Guy P. / Hair bundle defects and loss of function in the vestibular end organs of mice lacking the receptor-like inositol lipid phosphatase PTPRQ. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 8. pp. 2762-2772.
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