Extended Data Fig. 7: ZBP1 deficiency does not rescue the interferon response and pathology of Trex1^−/− mice.

a, Schematic depicting the generation of Trex1^−/− mice using CRISPR-Cas9-mediated gene targeting. Two gRNAs were used to delete the single coding exon of the Trex1 gene. DNA sequencing in homozygous mice confirmed the deletion. b, c, Immunoblot analysis of spleen (b) or heart (c) protein lysates from 8–10-week-old mice of the indicated genotypes with the indicated antibodies. α-tubulin and GAPDH were used as loading control. Lanes represent individual mice. One representative of two independent experiments is shown. d, Kaplan-Meier survival plot of mice of the indicated genotypes. Control mice include Trex1^WT/− Zbp1^−/− and Trex1^WT/WT Zbp1^−/− mice. e, Graph depicting body weight of 8–10-week-old mice of the indicated genotypes. Males: Trex1^−/− Zbp1^WT/WT (n = 7), Trex1^−/− Zbp1^−/− (n = 13), Trex1^−/− Zbp1^WT/− (n = 11), control (n = 15). Females: Trex1^−/− Zbp1^WT/WT (n = 9), Trex1^−/− Zbp1^−/− (n = 8), Trex1^−/− Zbp1^WT/− (n = 6), control (n = 8). Heart weight relative to body weight: Trex1^−/− Zbp1^WT/WT (n = 16), Trex1^−/− Zbp1^−/− (n = 21), Trex1^−/− Zbp1^WT/− (n = 17), control (n = 22). Spleen weight relative to body weight: Trex1^−/− Zbp1^WT/WT (n = 15), Trex1^−/− Zbp1^−/− (n = 18), Trex1^−/− Zbp1^WT/− (n = 10), control (n = 11). Control mice include Trex1^WT/− Zbp1^−/− and Trex1^WT/WT Zbp1^−/− mice. Dots represent individual mice, bar graphs show mean ± s.e.m and P values were calculated by one-way ANOVA test with Tukey’s correction for multiple comparison. f, Representative images of heart sections of 8–10-week-old Trex1^−/− Zbp1^WT/WT (n = 7), Trex1^−/− Zbp1^−/− (n = 8), Trex1^WT/− Zbp1^−/− (n = 5) and Trex1^WT/WT Zbp1^−/− (n = 5) mice stained with H&E or Masson’s Trichrome (collagen: blue, cytoplasm: red) or immunostained for CD45, CD3 or F4/80. Scale bars: 500 µm for H&E, CD45 and Masson’s Trichrome staining; 100 µm for CD3 and F4/80 staining. g, h, qRT-PCR analysis of mRNA expression of the indicated genes in heart tissues of 8–10-week-old mice of the indicated genotypes. Dots represent individual mice, bar graphs show mean ± s.e.m and P values were calculated by a Kruskal-Wallis test with Dunn’s multiple comparison. For gel source data, see Supplementary Figure 1.

Source data