In vitro and in vivo suppression of GJB2 expression by RNA interference

Yukihide Maeda; Kunihiro Fukushima; Kazunori Nishizaki; Richard J H Smith

doi:10.1093/hmg/ddi172

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In vitro and in vivo suppression of GJB2 expression by RNA interference

Journal article

Open access

Peer reviewed

In vitro and in vivo suppression of GJB2 expression by RNA interference

Yukihide Maeda, Kunihiro Fukushima, Kazunori Nishizaki and Richard J H Smith

Human molecular genetics, Vol.14(12), pp.1641-1650

06/15/2005

DOI: 10.1093/hmg/ddi172

PMID: 15857852

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https://doi.org/10.1093/hmg/ddi172View

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Abstract

Mutations in GJB2 (gap junction protein, beta-2) are the major cause of autosomal recessive non-syndromic hearing loss. A few allele variants of this gene also cause autosomal dominant non-syndromic hearing loss as a dominant-negative consequence of expression of the mutant protein. Allele-specific gene suppression by RNA interference (RNAi) is a potentially attractive strategy to prevent hearing loss caused by this mechanism. In this proof-of-principle study, we identified a potent GJB2-targeting short interfering RNA (siRNA) to post-transcriptionally silence the expression of the R75W allele variant of GJB2 in cultured mammalian cells. In a mouse model, this siRNA duplex selectively suppressed GJB2(R75W) expression by >70% of control levels, thereby preventing hearing loss. The level of endogenous murine Gjb2 expression was not affected. Our data show that RNAi can be used with specificity and efficiency in vivo to protect against hearing loss caused as a dominant-negative consequence of mutant gene expression.

Connexins - antagonists & inhibitors

Humans

Mice, Inbred C57BL

Connexins - genetics

Molecular Sequence Data

Sequence Homology, Nucleic Acid

Connexins - metabolism

Connexin 26

Hearing Loss - genetics

Hearing Loss - metabolism

Animals

Genes, Dominant

RNA Interference

Base Sequence

Female

Transcription, Genetic

Mice

Hearing Loss - prevention & control

Details

Title: Subtitle: In vitro and in vivo suppression of GJB2 expression by RNA interference
Creators: Yukihide Maeda - Molecular Otolaryngology Research Laboratory, Department of Otolaryngology-Head and Neck Surgery, Interdepartmental Ph.D. Genetics Program, The University of Iowa, 200 Hawkins Drive-21151 PFP, Iowa City, IA 52242, USA
Kunihiro Fukushima
Kazunori Nishizaki
Richard J H Smith
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.14(12), pp.1641-1650
DOI: 10.1093/hmg/ddi172
PMID: 15857852
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: DC03544 / NIDCD NIH HHS
Language: English
Date published: 06/15/2005
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: 9984007176502771

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