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

Kirk W Beisel; Sonia M Rocha-Sanchez; Ken A Morris; Liping Nie; Feng Feng; Bechara Kachar; Ebenezer N Yamoah; Bernd Fritzsch

doi:10.1523/JNEUROSCI.2110-05.2005

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

Journal article

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

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

The Journal of neuroscience, Vol.25(40), pp.9285-9293

10/05/2005

DOI: 10.1523/JNEUROSCI.2110-05.2005

PMCID: PMC6725753

PMID: 16207888

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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.

Animals, Newborn

Exons

Hearing Loss, High-Frequency - metabolism

Cochlea - cytology

Ganglia, Spinal - cytology

Mice, Inbred Strains

Hearing Loss, High-Frequency - genetics

Animals

Hair Cells, Auditory, Inner - metabolism

KCNQ Potassium Channels - metabolism

Gene Expression - physiology

RNA Splicing - genetics

Blotting, Northern - methods

Mice

Neurons, Afferent - metabolism

Gene Expression Regulation, Developmental - physiology

KCNQ Potassium Channels - genetics

Details

Title: Subtitle: Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss
Creators: Kirk W Beisel - Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, USA. beisel@creighton.edu
Sonia M Rocha-Sanchez
Ken A Morris
Liping Nie
Feng Feng
Bechara Kachar
Ebenezer N Yamoah
Bernd Fritzsch
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.25(40), pp.9285-9293
DOI: 10.1523/JNEUROSCI.2110-05.2005
PMID: 16207888
PMCID: PMC6725753
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Publisher: United States
Grant note: DC07592 / NIDCD NIH HHS R01 DC004279 / NIDCD NIH HHS R01 DC005009 / NIDCD NIH HHS R01 DC05009 / NIDCD NIH HHS DC04279 / NIDCD NIH HHS
Language: English
Date published: 10/05/2005
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070366802771

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