CRISPR-induced exon skipping is dependent on premature termination codon mutations

In previous studies, CRISPR/Cas9 was shown to induce unexpected exon skipping; however, the mechanism by which this phenomenon is triggered is controversial. By analyzing 22 gene-edited rabbit lines generated using CRISPR/Cas9, we provide evidence of exon skipping at high frequency in premature termination codon-mutated rabbits but not in the rabbits with a premature termination codon mutation in exon 1 rabbits with non-frameshift or missense mutations. Our results suggest that CRISPR-mediated exon skipping depends on premature termination codon mutation-induced nonsense-associated altered splicing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-018-1532-z) contains supplementary material, which is available to authorized users.