Extended Data Fig. 1: Characterisation of Adar^-/- Mavs^-/- Zbp1^{Zα1α2/Zα1α2} mice.

a, Numbers and percentages of pups obtained from Adar^+/- Mavs^-/- Zbp1^{+/+, +/ Zα1α2 or Zα1α2/Zα1α2} breeding pairs. Lower panels show representative images of 3 or 4 day old pups. Arrows indicate Adar/Mavs double knockout mice with the indicated Zbp1 genotypes. b, Sanger sequencing chromatograms of A-to-I editing sites in brain (Htr2c) or spleen (Mad2l1 and Rpa1) tissues derived from mice of the indicated genotypes. ADAR1-, ADAR2- and ADAR1/ADAR2-specific sites indicated by blue, red and purple triangles, respectively. c, Weight in grams (g) of 5 (P5) or 12 (P12) day old mice of the indicated genotypes. d, Weight in grams (g) of male mice of the indicated genotypes measured weekly from birth till 30 weeks of age. Right panel shows a representative picture of a 10 week old Adar^-/- Mavs^-/- Zbp1^{Zα1α2/Zα1α2} mouse and an Adar^+/+ Mavs^-/- Zbp1^{Zα1α2/Zα1α2} littermate. e, TUNEL assay on ileum sections from 1 week or 5 week old Adar^-/- Mavs^-/- mice expressing Zα domain mutant ZBP1 from one (Zbp1^+/Zα1α2) or two (Zbp1^{Zα1α2/Zα1α2}) alleles. Scale bar = 100 µm. f, quantification of TUNEL⁺ cells per crypt. Each data point in (c,d,f) represents an individual mouse. The numbers of mice (n) that were analysed per genotype in (c,d,f) are indicated in the graph. Lines in (c,f) represent the mean; P values by Mann-Whitney test. Lines in (d) represent a sigmoidal, 4PL fit; P values by two-way ANOVA

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