Vestibular dysfunction, altered macular structure and trait localization in A/J inbred mice

Sarath Vijayakumar, Teresa E. Lever, Jessica Pierce, Xing Zhao, David Bergstrom, Yunxia W Lundberg, Timothy A Jones, Sherri M Jones

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A/J mice develop progressive hearing loss that begins before 1 month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated that this strain also develops early onset vestibular dysfunction and has otoconial deficits. The purpose of this study was to characterize the vestibular dysfunction and macular structural pathology over the lifespan of A/J mice. Vestibular function was measured using linear vestibular evoked potentials (VsEPs). Macular structural pathology was evaluated using light microscopy, scanning electron microscopy, transmission electron microscopy, confocal microscopy and Western blotting. Individually, vestibular functional deficits in mice ranged from mild to profound. On average, A/J mice had significantly reduced vestibular sensitivity (elevated VsEP response thresholds and smaller amplitudes), whereas VsEP onset latency was prolonged compared to age-matched controls (C57BL/6). A limited age-related vestibular functional loss was also present. Structural analysis identified marked age-independent otoconial abnormalities in concert with some stereociliary bundle defects. Macular epithelia were incompletely covered by otoconial membranes with significantly reduced opacity and often contained abnormally large or giant otoconia as well as normal-appearing otoconia. Elevated expression of key otoconins (i.e., otoconin 90, otolin and keratin sulfate proteoglycan) ruled out the possibility of reduced levels contributing to otoconial dysgenesis. The phenotype of A/J was partially replicated in a consomic mouse strain (C57BL/6J-Chr 17A/J/NaJ), thus indicating that Chr 17A/J contained a trait locus for a new gene variant responsible to some extent for the A/J vestibular phenotype. Quantitative trait locus analysis identified additional epistatic influences associated with chromosomes 1, 4, 9 and X. Results indicate that the A/J phenotype represents a complex trait, and the A/J mouse strain presents a new model for the study of mechanisms underlying otoconial formation and maintenance.

Original languageEnglish (US)
Pages (from-to)154-172
Number of pages19
JournalMammalian Genome
Volume26
Issue number3-4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Inbred A Mouse
Evoked Potentials
Otolithic Membrane
Phenotype
Auditory Hair Cells
Pathology
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 1
Quantitative Trait Loci
Proteoglycans
Keratins
Transmission Electron Microscopy
Inbred C57BL Mouse
Hearing Loss
Confocal Microscopy
Electron Scanning Microscopy
Sulfates
Microscopy
Epithelium
Western Blotting

ASJC Scopus subject areas

  • Genetics

Cite this

Vestibular dysfunction, altered macular structure and trait localization in A/J inbred mice. / Vijayakumar, Sarath; Lever, Teresa E.; Pierce, Jessica; Zhao, Xing; Bergstrom, David; Lundberg, Yunxia W; Jones, Timothy A; Jones, Sherri M.

In: Mammalian Genome, Vol. 26, No. 3-4, 01.04.2015, p. 154-172.

Research output: Contribution to journalArticle

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