Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

Anand N Mhatre; Jiang Li; Arthur F Chen; C Spencer Yost; Richard J H Smith; Christoph H Kindler; Anil K Lalwani

doi:10.1002/jnr.10839

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Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

Journal article

Peer reviewed

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

Anand N Mhatre, Jiang Li, Arthur F Chen, C Spencer Yost, Richard J H Smith, Christoph H Kindler and Anil K Lalwani

Journal of neuroscience research, Vol.75(1), pp.25-31

01/01/2004

DOI: 10.1002/jnr.10839

PMID: 14689445

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Abstract

KCNK6 encodes a tandem pore domain potassium channel, TWIK-2, that maps to chromosome 19. Both STS and linkage maps established KCNK6 as a positional candidate gene for DFNA4, a form of autosomal dominant nonsyndromic hereditary hearing loss. Identification and characterization of Kcnk6 expression within the mammalian cochlea established the gene as a functional candidate for DFNA4. Identification of Twik-2 expression in the mouse cochlea was initially established via RT-PCR assay of cochlear RNA. Subsequent immunoblot analysis of cochlear homogenate yielded a distinct 35-kDa band corresponding to the calculated molecular weight of the mouse Twik-2. Immunohistochemical studies localized Twik-2 expression in the cochlea predominantly within the stria vascularis. This vascular tissue borders the cochlear duct and is a critical regulator of potassium concentration in the endolymph. Genomic structure of TWIK-2 was subsequently determined and shown to consist of three coding exons with splice acceptor and donor sites in accordance with the consensus GT-AG rule. Two separate DFNA4 families were screened for KCNK6 sequence alterations. No mutations were found, thus excluding TWIK-2 as the DFNA4 candidate disease gene. Nevertheless, expression of Twik-2 within the stria vascularis suggests a potential role for this protein as one of the terminal components of the potassium ion-recycling pathway that contributes toward its reabsorption into the endolymph.

Genomics

Blotting, Western - methods

Potassium Channels, Tandem Pore Domain

Humans

Myosin Type II

DNA Mutational Analysis - methods

RNA, Messenger - metabolism

Potassium Channels - genetics

Brain - metabolism

Hearing Loss - genetics

Immunohistochemistry - methods

Potassium Channels - metabolism

Carrier Proteins - genetics

Kidney - metabolism

Animals

Cochlea - metabolism

Chromosome Mapping - methods

Reverse Transcriptase Polymerase Chain Reaction - methods

Myosin Heavy Chains

Blotting, Northern - methods

Mice

Molecular Structure

Details

Title: Subtitle: Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4
Creators: Anand N Mhatre - Laboratory of Molecular Genetics, Epstein Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA. amhatre@med.nyu.edu
Jiang Li
Arthur F Chen
C Spencer Yost
Richard J H Smith
Christoph H Kindler
Anil K Lalwani
Resource Type: Journal article
Publication Details: Journal of neuroscience research, Vol.75(1), pp.25-31
DOI: 10.1002/jnr.10839
PMID: 14689445
NLM abbreviation: J Neurosci Res
ISSN: 0360-4012
eISSN: 1097-4547
Publisher: United States
Grant note: R01 DC03544 / NIDCD NIH HHS
Language: English
Date published: 01/01/2004
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006438202771

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