Cochlear function in mice with only one copy of the prestin gene

Mary Ann Cheatham*, Jing Zheng, K. H. Huynh, G. G. Du, J. Gao, J. Zuo, E. Navarrete, Peter Dallos

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency selectivity and outer hair cell (OHC) somatic electromotility. In addition, it has been reported by Liberman and colleagues that F2 generation heterozygotes exhibit a 6 dB reduction in sensitivity, as well as a decrease in protein and electromotility. Considering that the active process is non-linear, a halving of somatic electromotility would be expected to produce a much larger change in sensitivity. We therefore re-evaluated comparisons between heterozygotes and wildtype mice using both in vivo and in vitro electrophysiology, as well as molecular biology. Data reported here for F3-F5 generation mice indicate that compound action potential thresholds and tuning curves, as well as the cochlear microphonic, are similar in heterozygotes and wildtype controls. Measurements of non-linear capacitance in isolated OHCs demonstrate that charge density, as well as the voltage dependence and sensitivity of motor function, is indistinguishable in the two genotypes, as is somatic electromotility. In addition, both immunocytochemistry and western blot analysis in young adult mice suggest that prestin protein in heterozygotes is near normal. In contrast, prestin mRNA is always less than in wildtype mice at all ages tested. Results from F3-F5 generation mice suggest that one copy of the prestin gene is capable of compensating for the deleted copy and that heterozygous mice do not suffer peripheral hearing impairment.

Original languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalJournal of Physiology
Volume569
Issue number1
DOIs
StatePublished - Nov 15 2005

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Cochlea
Heterozygote
Genes
Outer Auditory Hair Cells
Electrophysiology
Gene Deletion
Hearing Loss
Action Potentials
Molecular Biology
Young Adult
Western Blotting
Immunohistochemistry
Genotype
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Cheatham, M. A., Zheng, J., Huynh, K. H., Du, G. G., Gao, J., Zuo, J., ... Dallos, P. (2005). Cochlear function in mice with only one copy of the prestin gene. Journal of Physiology, 569(1), 229-241. https://doi.org/10.1113/jphysiol.2005.093518
Cheatham, Mary Ann ; Zheng, Jing ; Huynh, K. H. ; Du, G. G. ; Gao, J. ; Zuo, J. ; Navarrete, E. ; Dallos, Peter. / Cochlear function in mice with only one copy of the prestin gene. In: Journal of Physiology. 2005 ; Vol. 569, No. 1. pp. 229-241.
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abstract = "Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency selectivity and outer hair cell (OHC) somatic electromotility. In addition, it has been reported by Liberman and colleagues that F2 generation heterozygotes exhibit a 6 dB reduction in sensitivity, as well as a decrease in protein and electromotility. Considering that the active process is non-linear, a halving of somatic electromotility would be expected to produce a much larger change in sensitivity. We therefore re-evaluated comparisons between heterozygotes and wildtype mice using both in vivo and in vitro electrophysiology, as well as molecular biology. Data reported here for F3-F5 generation mice indicate that compound action potential thresholds and tuning curves, as well as the cochlear microphonic, are similar in heterozygotes and wildtype controls. Measurements of non-linear capacitance in isolated OHCs demonstrate that charge density, as well as the voltage dependence and sensitivity of motor function, is indistinguishable in the two genotypes, as is somatic electromotility. In addition, both immunocytochemistry and western blot analysis in young adult mice suggest that prestin protein in heterozygotes is near normal. In contrast, prestin mRNA is always less than in wildtype mice at all ages tested. Results from F3-F5 generation mice suggest that one copy of the prestin gene is capable of compensating for the deleted copy and that heterozygous mice do not suffer peripheral hearing impairment.",
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Cheatham, MA, Zheng, J, Huynh, KH, Du, GG, Gao, J, Zuo, J, Navarrete, E & Dallos, P 2005, 'Cochlear function in mice with only one copy of the prestin gene', Journal of Physiology, vol. 569, no. 1, pp. 229-241. https://doi.org/10.1113/jphysiol.2005.093518

Cochlear function in mice with only one copy of the prestin gene. / Cheatham, Mary Ann; Zheng, Jing; Huynh, K. H.; Du, G. G.; Gao, J.; Zuo, J.; Navarrete, E.; Dallos, Peter.

In: Journal of Physiology, Vol. 569, No. 1, 15.11.2005, p. 229-241.

Research output: Contribution to journalArticle

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