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

被引：0
作者：
F Han
H Yu
C Tian
H E Chen
C Benedict-Alderfer
Y Zheng
Q Wang
X Han
Q Y Zheng
机构：
[1] Case Western Reserve University,Department of Otolaryngology
[2] Case Western Reserve University,HNS
[3] Case Comprehensive Cancer Center,Department of Genetics
[4] Case Western Reserve University,undefined
[5] 5Current address: Department of Otolaryngology and HNS,undefined
[6] Chinese PLA Institute of Otolaryngology,undefined
[7] Chinese PLA General Hospital,undefined
[8] 28 Fuxing Road,undefined
[9] Beijing 100853 China.,undefined
来源：
The Pharmacogenomics Journal | 2012年 / 12卷
关键词：
mouse model; mutation; hearing loss; apoptosis; Z-VAD-FMK;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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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页码：30 / 44
页数：14
相关论文
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