A New Mouse Mutant of the Cdh23 Gene with Early-onset Hearing Loss Facilitates Evaluation of Otoprotection Drugs

Overview

Journal Pharmacogenomics J

Specialties Genetics
Molecular Biology
Pharmacology

Date 2010 Jul 21

PMID 20644563

Citations 29

Authors

F Han

H Yu

C Tian

H E Chen

C Benedict-Alderfer

Y Zheng

Q Wang

X Han

Q Y Zheng

Affiliations

Soon will be listed here.

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.

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