Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice.
Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice.
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CIB2 缺失会导致小鼠严重听力损失并消除机械电传导。
DOI：
10.3389/fnmol.2017.00401
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发表时间：
2017
影响因子：
4.8
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Wang Y;Li J;Yao X;Li W;Du H;Tang M;Xiong W;Chai R;Xu Z
钙和整合素结合蛋白2（CIB 2）属于具有四个已知成员CIB 1至CIB 4的蛋白质家族，其特征在于多个钙结合EF-手结构域。在家族成员中，Cib 1和Cib 2基因在小鼠耳蜗毛细胞中表达，并且人CIB 2基因的突变与非综合征性耳聋DFNB 48和综合征性耳聋USH 1 J相关。为了进一步探索CIB 1和CIB 2在听力中的功能，我们使用成簇规则间隔短回文重复序列（CRISPR）相关Cas9核酸酶（CRISPR/Cas9）基因组编辑技术建立了Cib 1和Cib 2敲除小鼠。我们发现，CIB 1蛋白的丢失不会影响听觉功能，而CIB 2蛋白的丢失会导致小鼠严重的听力损失。进一步的研究表明，毛细胞静纤毛的发展受到影响，在Cib 2基因敲除小鼠。值得注意的是，CIB 2的缺失消除了听觉毛细胞中的机械电转导（MET）电流。总之，我们在这里表明，虽然CIB 1和CIB 2都很容易在耳蜗中检测到，只有CIB 2的损失导致严重的听力损失，CIB 2是必不可少的听觉毛细胞MET。
Calcium and integrin-binding protein 2 (CIB2) belongs to a protein family with four known members, CIB1 through CIB4, which are characterized by multiple calcium-binding EF-hand domains. Among the family members, the Cib1 and Cib2 genes are expressed in mouse cochlear hair cells, and mutations in the human CIB2 gene have been associated with nonsyndromic deafness DFNB48 and syndromic deafness USH1J. To further explore the function of CIB1 and CIB2 in hearing, we established Cib1 and Cib2 knockout mice using the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease (CRISPR/Cas9) genome editing technique. We found that loss of CIB1 protein does not affect auditory function, whereas loss of CIB2 protein causes profound hearing loss in mice. Further investigation revealed that hair cell stereocilia development is affected in Cib2 knockout mice. Noticeably, loss of CIB2 abolishes mechanoelectrical transduction (MET) currents in auditory hair cells. In conclusion, we show here that although both CIB1 and CIB2 are readily detected in the cochlea, only loss of CIB2 results in profound hearing loss, and that CIB2 is essential for auditory hair cell MET.
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影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
DOI：
10.1186/1478-811x-10-20
发表时间：
2012-07-12
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Ceriani F;Mammano F
通讯作者：
Mammano F
影响因子：
6.7
作者：
DeNofrio, Jan C.;Yuan, Weiping;Parise, Leslie V.
通讯作者：
Parise, Leslie V.
影响因子：
16.6
作者：
Giese APJ;Tang YQ;Sinha GP;Bowl MR;Goldring AC;Parker A;Freeman MJ;Brown SDM;Riazuddin S;Fettiplace R;Schafer WR;Frolenkov GI;Ahmed ZM
通讯作者：
Ahmed ZM
影响因子：
15.9
作者：
Kawashima, Yoshiyuki;Geleoc, Gwenaelle S. G.;Griffith, Andrew J.
通讯作者：
Griffith, Andrew J.