| First Author | Liu X | Year | 2018 |
| Journal | G3 (Bethesda) | Volume | 8 |
| Issue | 10 | Pages | 3221-3230 |
| PubMed ID | 30082328 | Mgi Jnum | J:274170 |
| Mgi Id | MGI:6296523 | Doi | 10.1534/g3.118.200405 |
| Citation | Liu X, et al. (2018) Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice. G3 (Bethesda) 8(10):3221-3230 |
| abstractText | 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. |
