The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice.
Document Type
Article
Publication Date
2010
Keywords
Amino-Acid-Substitution, Animals, Base-Sequence, Cadherins, Carrier-Proteins, Chick-Embryo, Disease-Models-Animal, Disease-Progression, Evoked-Potentials-Auditory, Hair-Cells-Auditory-Inner, Hearing-Loss, Mice, Mice-Inbred-DBA, Microfilament-Proteins, Molecular-Sequence-Data, Mutation-Missense, Polymorphism-Genetic, Saccule-and-Utricle, Xenopus-laevis
First Page
9683
Last Page
9694
JAX Source
J Neurosci 2010 Jul; 30(29):9683-94.
Abstract
The quantitative trait locus ahl8 is a key contributor to the early-onset, age-related hearing loss of DBA/2J mice. A nonsynonymous nucleotide substitution in the mouse fascin-2 gene (Fscn2) is responsible for this phenotype, confirmed by wild-type BAC transgene rescue of hearing loss in DBA/2J mice. In chickens and mice, FSCN2 protein is abundant in hair-cell stereocilia, the actin-rich structures comprising the mechanically sensitive hair bundle, and is concentrated toward stereocilia tips of the bundle's longest stereocilia. FSCN2 expression increases when these stereocilia differentially elongate, suggesting that FSCN2 controls filament growth, stiffens exposed stereocilia, or both. Because ahl8 accelerates hearing loss only in the presence of mutant cadherin 23, a component of hair-cell tip links, mechanotransduction and actin crosslinking must be functionally interrelated.
Recommended Citation
Shin JB,
Longo GC,
Gagnon LH,
Spinelli KJ,
Pagana JM,
Wilmarth PA,
David LL,
Gillespie PG,
Johnson KR.
The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. J Neurosci 2010 Jul; 30(29):9683-94.