Hearing and vestibular deficits in the Coch-/- null mouse model: Comparison to the CochG88E/G88E mouse and to DFNA9 hearing and balance disorder

Sherri M. Jones, Nahid G. Robertson, Shelly Given, Anne B.S. Giersch, M. Charles Liberman, Cynthia C. Morton

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Two mouse models, the CochG88E/G88E or " knock-in" and the Coch-/- or " knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch-/- and CochG88E/G88E mouse models. Both Coch-/- and CochG88E/G88E mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch-/- mice and 4 of 8 CochG88E/G88E mice have absent ABRs. Interestingly Coch-/+ mice do not show hearing deficits, in contrast to CochG88E/+, which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch-/- mice at 13 and 21 months, the two ages tested, and as early as seven months in the CochG88E/G88E mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalHearing Research
Volume272
Issue number1-2
DOIs
StatePublished - Feb 1 2011

Fingerprint

Hearing Disorders
Hearing
Evoked Potentials
Brain Stem Auditory Evoked Potentials
Haploinsufficiency
Blood Coagulation Factors
Sensorineural Hearing Loss
Sequence Deletion
Age Factors
Cochlea
Inner Ear
Hearing Loss
Analysis of Variance
Genotype

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Hearing and vestibular deficits in the Coch-/- null mouse model : Comparison to the CochG88E/G88E mouse and to DFNA9 hearing and balance disorder. / Jones, Sherri M.; Robertson, Nahid G.; Given, Shelly; Giersch, Anne B.S.; Liberman, M. Charles; Morton, Cynthia C.

In: Hearing Research, Vol. 272, No. 1-2, 01.02.2011, p. 42-48.

Research output: Contribution to journalArticle

Jones, Sherri M. ; Robertson, Nahid G. ; Given, Shelly ; Giersch, Anne B.S. ; Liberman, M. Charles ; Morton, Cynthia C. / Hearing and vestibular deficits in the Coch-/- null mouse model : Comparison to the CochG88E/G88E mouse and to DFNA9 hearing and balance disorder. In: Hearing Research. 2011 ; Vol. 272, No. 1-2. pp. 42-48.
@article{fd440d4487684c8c91052ef2084eac2b,
title = "Hearing and vestibular deficits in the Coch-/- null mouse model: Comparison to the CochG88E/G88E mouse and to DFNA9 hearing and balance disorder",
abstract = "Two mouse models, the CochG88E/G88E or {"} knock-in{"} and the Coch-/- or {"} knock-out{"} (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch-/- and CochG88E/G88E mouse models. Both Coch-/- and CochG88E/G88E mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch-/- mice and 4 of 8 CochG88E/G88E mice have absent ABRs. Interestingly Coch-/+ mice do not show hearing deficits, in contrast to CochG88E/+, which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch-/- mice at 13 and 21 months, the two ages tested, and as early as seven months in the CochG88E/G88E mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.",
author = "Jones, {Sherri M.} and Robertson, {Nahid G.} and Shelly Given and Giersch, {Anne B.S.} and Liberman, {M. Charles} and Morton, {Cynthia C.}",
year = "2011",
month = "2",
day = "1",
doi = "10.1016/j.heares.2010.11.002",
language = "English (US)",
volume = "272",
pages = "42--48",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Hearing and vestibular deficits in the Coch-/- null mouse model

T2 - Comparison to the CochG88E/G88E mouse and to DFNA9 hearing and balance disorder

AU - Jones, Sherri M.

AU - Robertson, Nahid G.

AU - Given, Shelly

AU - Giersch, Anne B.S.

AU - Liberman, M. Charles

AU - Morton, Cynthia C.

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Two mouse models, the CochG88E/G88E or " knock-in" and the Coch-/- or " knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch-/- and CochG88E/G88E mouse models. Both Coch-/- and CochG88E/G88E mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch-/- mice and 4 of 8 CochG88E/G88E mice have absent ABRs. Interestingly Coch-/+ mice do not show hearing deficits, in contrast to CochG88E/+, which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch-/- mice at 13 and 21 months, the two ages tested, and as early as seven months in the CochG88E/G88E mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.

AB - Two mouse models, the CochG88E/G88E or " knock-in" and the Coch-/- or " knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch-/- and CochG88E/G88E mouse models. Both Coch-/- and CochG88E/G88E mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch-/- mice and 4 of 8 CochG88E/G88E mice have absent ABRs. Interestingly Coch-/+ mice do not show hearing deficits, in contrast to CochG88E/+, which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch-/- mice at 13 and 21 months, the two ages tested, and as early as seven months in the CochG88E/G88E mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.

UR - http://www.scopus.com/inward/record.url?scp=79751527116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79751527116&partnerID=8YFLogxK

U2 - 10.1016/j.heares.2010.11.002

DO - 10.1016/j.heares.2010.11.002

M3 - Article

C2 - 21073934

AN - SCOPUS:79751527116

VL - 272

SP - 42

EP - 48

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

IS - 1-2

ER -