The ATG16L1 risk variant is associated with loss of intestinal organoid viability and virally triggered disease. (A and B) Viability of organoids from B6 and Atg16L1^T316A (T316A) mice treated ± TNFα and Nec-1. n = 3 mice each (A). Representative H&E images and quantification of Paneth cells per organoid on day 7 normalized to total IECs (B). TNFα was added on day 0. Arrowheads indicate Paneth cells. At least 20 organoids were analyzed from three mice each. Bars, 50 µm. (C) Survival of B6 and Atg16L1^T316A (T316A) mice treated with 5% DSS ± MNV infection. n = 8 (f/f), 8 (T316A), 9 (f/f + MNV), and 16 (T316A + MNV). Data points in A are mean of three technical replicates, and data points in B represent individual organoids. Bars represent mean ± SEM, and at least two independent experiments were performed. *, P < 0.05; **, P < 0.01 by unpaired t test in A, one-way ANOVA and Tukey’s test in B, and Mantel-Cox in C.