Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2018-10-01
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| Series: | G3: Genes, Genomes, Genetics |
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| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.118.200405 |
| _version_ | 1818658475777982464 |
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| author | Xiang Liu Mengmeng Zhao Yi Xie Ping Li Oumei Wang Bingxin Zhou Linlin Yang Yao Nie Lin Cheng Xicheng Song Changzhu Jin Fengchan Han |
| author_facet | Xiang Liu Mengmeng Zhao Yi Xie Ping Li Oumei Wang Bingxin Zhou Linlin Yang Yao Nie Lin Cheng Xicheng Song Changzhu Jin Fengchan Han |
| author_sort | Xiang Liu |
| collection | DOAJ |
| description | 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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| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-17T03:57:58Z |
| publishDate | 2018-10-01 |
| publisher | Oxford University Press |
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| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-92cf96dfdc924547b2f8941e4d8d179c2022-12-21T22:04:35ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362018-10-018103221323010.1534/g3.118.2004059Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J MiceXiang LiuMengmeng ZhaoYi XiePing LiOumei WangBingxin ZhouLinlin YangYao NieLin ChengXicheng SongChangzhu JinFengchan HanFascin2 (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.http://g3journal.org/lookup/doi/10.1534/g3.118.200405Fascin2mutationTALENhearing losshair cellretinitis pigmentosa |
| spellingShingle | Xiang Liu Mengmeng Zhao Yi Xie Ping Li Oumei Wang Bingxin Zhou Linlin Yang Yao Nie Lin Cheng Xicheng Song Changzhu Jin Fengchan Han Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice G3: Genes, Genomes, Genetics Fascin2 mutation TALEN hearing loss hair cell retinitis pigmentosa |
| title | Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice |
| title_full | Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice |
| title_fullStr | Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice |
| title_full_unstemmed | Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice |
| title_short | Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice |
| title_sort | null mutation of the fascin2 gene by talen leading to progressive hearing loss and retinal degeneration in c57bl 6j mice |
| topic | Fascin2 mutation TALEN hearing loss hair cell retinitis pigmentosa |
| url | http://g3journal.org/lookup/doi/10.1534/g3.118.200405 |
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