Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss

Kirk Beisel, Sonia Rocha-Sanchez, Ken A. Morris, Liping Nie, Feng Feng, Bechara Kachar, Ebenezer N. Yamoah, Bernd Fritzsch

Research output: Contribution to journalArticle

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Abstract

Human KCNQ4 mutations known as DFNA2 cause non-syndromic, autosomal-dominant, progressive high-frequency hearing loss in which the cellular and molecular basis is unclear. We provide immunofluorescence data showing that Kcnq4 expression in the adult cochlea has both longitudinal (base to apex) and radial (inner to outer hair cells) gradients. The most intense labeling is in outer hair cells at the apex and in inner hair cells as well as spiral ganglion neurons at the base. Spatiotemporal expression studies show increasing intensity of KCNQ4 protein labeling from postnatal day 21 (P21) to P120 mice that is most apparent in inner hair cells of the middle turn. We have identified four alternative splice variants of Kcnq4 in mice. The alternative use of exons 9-11 produces three transcript variants (v1-v3), whereas the fourth variant (v4) skips all three exons; all variants have the same amino acid sequence at the C termini. Both reverse transcription-PCR and quantitative PCR analyses demonstrate that these variants have differential expression patterns along the length of the mouse organ of Corti and spiral ganglion neurons. Our expression data suggest that the primary defect leading to high-frequency loss in DFNA2 patients may be attributable to high levels of the dysfunctional Kcnq4_v3 variant in the spiral ganglion and inner hair cells in the basal hook region. Progressive hearing loss associated with aging may result from an increasing mutational load expansion toward the apex in inner hair cells and spiral ganglion neurons.

Original languageEnglish
Pages (from-to)9285-9293
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number40
DOIs
StatePublished - Oct 5 2005

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Inner Auditory Hair Cells
High-Frequency Hearing Loss
Spiral Ganglion
Sensory Receptor Cells
Outer Auditory Hair Cells
Neurons
Exons
Organ of Corti
Polymerase Chain Reaction
Cochlea
Hearing Loss
Reverse Transcription
Fluorescent Antibody Technique
Amino Acid Sequence
Mutation
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss. / Beisel, Kirk; Rocha-Sanchez, Sonia; Morris, Ken A.; Nie, Liping; Feng, Feng; Kachar, Bechara; Yamoah, Ebenezer N.; Fritzsch, Bernd.

In: Journal of Neuroscience, Vol. 25, No. 40, 05.10.2005, p. 9285-9293.

Research output: Contribution to journalArticle

Beisel, Kirk ; Rocha-Sanchez, Sonia ; Morris, Ken A. ; Nie, Liping ; Feng, Feng ; Kachar, Bechara ; Yamoah, Ebenezer N. ; Fritzsch, Bernd. / Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 40. pp. 9285-9293.
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