| First Author | Charton K | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 20 | Pages | 4518-4532 |
| PubMed ID | 28173117 | Mgi Jnum | J:238648 |
| Mgi Id | MGI:5823313 | Doi | 10.1093/hmg/ddw280 |
| Citation | Charton K, et al. (2016) Exploiting the CRISPR/Cas9 system to study alternative splicing in vivo: application to titin. Hum Mol Genet 25(20):4518-4532 |
| abstractText | The giant protein titin is the third most abundant protein in striated muscle. Mutations in its gene are responsible for diseases affecting the cardiac and/or the skeletal muscle. Titin has been reported to be expressed in multiple isoforms with considerable variability in the I-band, ensuring the modulation of the passive mechanical properties of the sarcomere. In the M-line, only the penultimate Mex5 exon coding for the specific is7 domain has been reported to be subjected to alternative splicing. Using the CRISPR-Cas9 editing technology, we generated a mouse model where we stably prevent the expression of alternative spliced variant(s) carrying the corresponding domain. Interestingly, the suppression of the domain induces a phenotype mostly in tissues usually expressing the isoform that has been suppressed, indicating that it fulfills (a) specific function(s) in these tissues allowing a perfect adaptation of the M-line to physiological demands of different muscles. |
