Details

Autor(en) / Beteiligte

• Charton, Karine
• Suel, Laurence
• Henriques, Sara F
• Moussu, Jean-Paul
• Bovolenta, Matteo
• Taillepierre, Miguel
• Becker, Céline
• Lipson, Karelia
• Richard, Isabelle

Titel

Exploiting the CRISPR/Cas9 system to study alternative splicing in vivo: application to titin

Ist Teil von

• Human molecular genetics, 2016-10, Vol.25 (20), p.4518-4532

Ort / Verlag

England: Oxford University Press (OUP)

Erscheinungsjahr

2016

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.