A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs.

The Pharmacogenomics Journal
F HanQ Y Zheng

Abstract

We report a novel mutation (erlong, erl) of the cadherin 23 (Cdh23) gene in a mouse model for DFNB12 characterized by progressive hearing loss beginning from postnatal day 27 (P27). Genetic and sequencing analysis revealed a 208 T >C transition causing an amino-acid substitution (70S-P). Caspase expression was upregulated in mutant inner ears. Hearing was preserved (up to 35-dB improvement) in pan-caspase inhibitor Z-VAD-FMK-treated mutants compared with untreated mutants (P<0.05). Outer hair cell (OHC) loss in the cochleae of Z-VAD-FMK-treated mutants was significantly reduced compared with those of untreated mice. Thus, the erl mutation can lead to hearing loss through apoptosis. This is the first genetic mouse model of hearing loss shown to respond to otoprotective drug therapy. The short interval from initial hearing loss to deafness (P27-P90) makes this model ideal for screening and validating otoprotective drugs.

References

Jan 1, 1996·Methods in Enzymology·J GarnierB Robson
Jan 1, 1997·Mammalian Genome : Official Journal of the International Mammalian Genome Society·E C BrydaL Flaherty
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A S YapB M Gumbiner
Feb 3, 1998·Hearing Research·K R JohnsonQ Y Zheng
Mar 10, 2001·Molecular and Cellular Biology·M AzamA H Chishti
Apr 27, 2001·Biochemical and Biophysical Research Communications·T WadaR Kominami
Sep 12, 2001·Journal of the Association for Research in Otolaryngology : JARO·S Hequembourg, M C Liberman
May 20, 2003·Immunological Reviews·Emma M CreaghSeamus J Martin
Jun 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lars ZenderStefan Kubicka
Apr 2, 2004·Nature·Jan SiemensUlrich Müller
Dec 14, 2004·Human Molecular Genetics·Avital AdatoChristine Petit
Apr 4, 2006·Brain Research·Kenneth R JohnsonKonrad Noben-Trauth
Jan 11, 2007·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Dylan K ChanMichael G Kaplitt
Feb 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shuping JiaDavid Z Z He
Feb 19, 2008·Neurobiology of Aging·Qing Yin ZhengKenneth R Johnson
Mar 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Martin SchwanderUlrich Müller
Jul 20, 2010·The Laryngoscope·Sami J MelkiCliff A Megerian

❮ Previous
Next ❯

Citations

Oct 3, 2013·PloS One·Kerry A MillerShehnaaz S M Manji
Mar 8, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ruishuang GengKumar N Alagramam
Mar 7, 2013·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Maroun T SemaanCliff A Megerian
May 25, 2015·Hearing Research·Linlin YangFengchan Han
Feb 7, 2013·Neuroscience·F HanQ Y Zheng
Mar 8, 2017·Clinical and Experimental Otorhinolaryngology·Lixiang GaoFengchan Han
Aug 30, 2017·Cold Spring Harbor Perspectives in Biology·Avinash JaiganeshMarcos Sotomayor
Apr 14, 2020·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Shanshan HuangFengchan Han
Mar 28, 2017·Journal of Neuroscience Research·Qingzhu WangQingyin Zheng
Jun 1, 2017·International Journal of Molecular Medicine·Lu SangQingyin Zheng
Dec 4, 2020·The Biochemical Journal·Surbhi GargSabyasachi Rakshit
Nov 17, 2020·Frontiers in Genetics·Meg WhatleyElaine Y M Wong

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
electrophoresis
genotyping

Software Mentioned

ImageJ
GOR IV
Ensemble
IHS Smart EP

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis