Establishment of the Nudt15^−/−mouse model using CRISPR-Cas9–mediated genome editing. (A) Mouse wild-type Nudt15 gene consists of 5 exons, and the start codon is located in exon 3 (top panel). Magnified region describes sgRNA target sequence in Nudt15 (red) and the protospacer adjacent motif (PAM) sequence (blue; bottom panel). (B) A single base insertion of c.78_79insT (red arrows) was created, resulting in frameshift and loss of functional Nudt15.