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 Wilmarth, Larry David, Peter Barr-Gillespie, Kenneth R. Johnson

Research output: Contribution to journalArticle

77 Citations (Scopus)

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

Fingerprint

Stereocilia
Inbred DBA Mouse
Hearing Loss
Hair
Actins
Quantitative Trait Loci
Cellular Structures
Cadherins
Transgenes
Age of Onset
Chickens
Nucleotides
fascin
Phenotype
Growth
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. / Shin, Jung Bum; Longo-Guess, Chantal M.; Gagnon, Leona H.; Saylor, Katherine W.; Dumont, Rachel A.; Spinelli, Kateri J.; Pagana, James M.; Wilmarth, Phillip; David, Larry; Barr-Gillespie, Peter; Johnson, Kenneth R.

In: Journal of Neuroscience, Vol. 30, No. 29, 21.07.2010, p. 9683-9694.

Research output: Contribution to journalArticle

Shin, Jung Bum ; Longo-Guess, Chantal M. ; Gagnon, Leona H. ; Saylor, Katherine W. ; Dumont, Rachel A. ; Spinelli, Kateri J. ; Pagana, James M. ; Wilmarth, Phillip ; David, Larry ; Barr-Gillespie, Peter ; Johnson, Kenneth R. / The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 29. pp. 9683-9694.
@article{a52d3528d7df4364875f2aba076d3840,
title = "The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice",
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.",
author = "Shin, {Jung Bum} and Longo-Guess, {Chantal M.} and Gagnon, {Leona H.} and Saylor, {Katherine W.} and Dumont, {Rachel A.} and Spinelli, {Kateri J.} and Pagana, {James M.} and Phillip Wilmarth and Larry David and Peter Barr-Gillespie and Johnson, {Kenneth R.}",
year = "2010",
month = "7",
day = "21",
doi = "10.1523/JNEUROSCI.1541-10.2010",
language = "English (US)",
volume = "30",
pages = "9683--9694",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "29",

}

TY - JOUR

T1 - The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice

AU - Shin, Jung Bum

AU - Longo-Guess, Chantal M.

AU - Gagnon, Leona H.

AU - Saylor, Katherine W.

AU - Dumont, Rachel A.

AU - Spinelli, Kateri J.

AU - Pagana, James M.

AU - Wilmarth, Phillip

AU - David, Larry

AU - Barr-Gillespie, Peter

AU - Johnson, Kenneth R.

PY - 2010/7/21

Y1 - 2010/7/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77954847853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954847853&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1541-10.2010

DO - 10.1523/JNEUROSCI.1541-10.2010

M3 - Article

VL - 30

SP - 9683

EP - 9694

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 29

ER -