The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice

Jung Bum Shin, Chantal M. Longo-Guess, Leona H. Gagnon, Katherine W. Saylor, Rachel A. Dumont, Kateri J. Spinelli, James M. Pagana, Phillip A. Wilmarth, Larry L. David, Peter G. Gillespie, Kenneth R. Johnson

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9683-9694
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number29
DOIs
StatePublished - Jul 21 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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