Generation of Gsdme −/− and Gsdmd −/− mice. (A and B) Schematics depicting the generation of mice that are deficient for GSDME (A) or GSDMD (B) using CRISPR-Cas9–mediated gene targeting in C57BL/6N zygotes, as indicated. To generate Gsdme−/− mice, exon 7 was targeted, resulting in a 4-bp deletion and therefore a frameshift and a premature stop codon indicated with a star (*). To generate Gsdmd−/− mice, exon 3 was targeted by two gRNAs, resulting in a 105-bp deletion and a frameshift in exon 3. The new premature stop codon is indicated with a star (*). The resulting deletions were confirmed by Sanger sequencing.