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- Title
Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice.
- Authors
Xiang Liu; Mengmeng Zhao; Yi Xie; Ping Li; Oumei Wang; Bingxin Zhou; Linlin Yang; Yao Nie; Lin Cheng; Xicheng Song; Changzhu Jin; Fengchan Han
- Abstract
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 Fscn -/- mice. As a result, the Fscn -/- 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 -4 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn -/- mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn -/- 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.
- Subjects
NULL mutation; HEARING disorders; RETINAL degeneration
- Publication
G3: Genes | Genomes | Genetics, 2018, Vol 8, Issue 10, p3221
- ISSN
2160-1836
- Publication type
Article
- DOI
10.1534/g3.118.200405