An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.
An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.
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DOI：
10.1038/ng.369
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发表时间：
2009-05
期刊：
影响因子：
30.8
通讯作者：
Steel, Karen P.
中科院分区：
文献类型：
--
作者：
Lewis, Morag A.;Quint, Elizabeth;Glazier, Anne M.;Fuchs, Helmut;De Angelis, Martin Hrabe;Langford, Cordelia;van Dongen, Stijn;Abreu-Goodger, Cei;Piipari, Matias;Redshaw, Nick;Dalmay, Tamas;Angel Moreno-Pelayo, Miguel;Enright, Anton J.;Steel, Karen P.
进行性听力损失在人类中很常见，但对其分子基础知之甚少。我们报告了一个新的ENU诱导的小鼠突变株Dinuendo，该突变在Mirn96的种子区发生了单碱基变化。杂合子表现为进行性听力损失和毛细胞异常，而纯合子没有耳蜗反应。大多数microRNAs被认为通过与其mRNAs上的特定位点结合而下调靶基因，因此种子的突变应该导致靶基因上调。基因芯片分析显示，96个转录本在纯合子中的表达发生了显著变化；值得注意的是，SLC26A5、肿瘤调节蛋白、Gfi1、Ptprq和Pitpnm1表达下调。超几何p值分析表明，数百个基因在突变体中上调。不同的基因，其靶点与突变种子互补，表达下调。这是第一个被发现与耳聋有关的微RNA，而且Dinuendo代表了一个模型，可以更普遍地理解和潜在地减缓听力损失中毛细胞的进行性退化。
Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new ENU-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, while homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, oncomodulin, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric p-value analysis showed hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally.
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影响因子：
3.5
作者：
Duan, Ranhui;Pak, ChangHui;Jin, Peng
通讯作者：
Jin, Peng
影响因子：
30.8
作者：
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作者：
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Zuo, Jian
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通讯作者：
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