Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice.
Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice.
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TALEN 对 Fascin2 基因的无效突变导致 C57BL/6J 小鼠进行性听力丧失和视网膜变性
DOI：
10.1534/g3.118.200405
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发表时间：
2018-10-03
期刊：
影响因子：
--
通讯作者：
Han F
中科院分区：
文献类型：
--
作者：
Liu X;Zhao M;Xie Y;Li P;Wang O;Zhou B;Yang L;Nie Y;Cheng L;Song X;Jin C;Han F
束蛋白2（FSCN2）是一种肌动蛋白交联蛋白，主要定位于视网膜以及毛细胞的静纤毛中。早期研究表明，人FASCIN2（FSCN2）基因的缺失突变可导致常染色体显性遗传性视网膜色素变性。近期研究显示，小鼠Fscn2基因的一个错义突变（R109H）可导致DBA/2J小鼠听力过早丧失。为了探究该基因的功能，在C57BL/6J背景下利用转录激活因子样效应物核酸酶（TALEN）敲除了Fscn2。培育出了在Fscn2目标区域分别缺失1、4、5和41个核苷酸的4种小鼠品系。携带相同的41个核苷酸缺失的F1杂合子（Fscn2+/-）小鼠进行交配以产生Fscn2 -/-小鼠。结果，通过听觉脑干反应阈值升高检测发现，Fscn2 -/-小鼠表现出进行性听力丧失。听力损伤在3周龄时于高刺激频率下开始出现，并在24周龄时最为严重。此外，通过F - 肌动蛋白染色和扫描电子显微镜观察发现，Fscn2 -/-小鼠的毛细胞退化以及静纤毛缺失现象明显。而且，与对照组相比，在8、16和24周时，Fscn2 -/-小鼠的视网膜电图振幅显著降低且视网膜变薄。这些结果表明，在C57BL/6J小鼠中，Fscn2对于维持耳和眼的功能至关重要，并且Fscn2的无效突变会导致进行性听力丧失和视网膜变性。
Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 (FSCN2) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous (Fscn2+/−) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2−/− mice. As a result, the Fscn2−/− mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2−/− mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2−/− mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration.
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影响因子：
3.3
作者：
Han F;Yu H;Zheng T;Ma X;Zhao X;Li P;Le L;Su Y;Zheng QY
通讯作者：
Zheng QY
影响因子：
2.4
作者：
Suzuki S;Ishikawa M;Ueda T;Ohshiba Y;Miyasaka Y;Okumura K;Yokohama M;Taya C;Matsuoka K;Kikkawa Y
通讯作者：
Kikkawa Y
DOI：
10.1002/ar.22579
发表时间：
2012-11
期刊：
Anatomical record (Hoboken, N.J. : 2007)
影响因子：
--
作者：
Angeli S;Lin X;Liu XZ
通讯作者：
Liu XZ
影响因子：
2.9
作者：
Noben-Trauth K;Johnson KR
通讯作者：
Johnson KR
影响因子：
168.9
作者：
Gates, GA;Mills, JH
通讯作者：
Mills, JH