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. 2022 Nov 8;220(1):e20220829. doi: 10.1084/jem.20220829

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© 2022 Schumann et al.

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Figure 1. — Low-level chronic DNA damage in SAMHD1-deficient mice. (A) GSEA against the Reactome gene set collection (MSigDB) showing that exclusively gene sets of immune pathways (blue) and DNA replication (red) are enriched in Samhd1^Δ/Δ vs. Samhd1^+/+ peritoneal macrophages. NES, normalized enrichment score. (B) CTNF of the γH2AX signal in pre-senescent primary MEFs and CD11b⁺F4/80^HI peritoneal macrophages of the indicated genotypes (Student’s t test) and representative immunofluorescence pictures. Scale bars = 10 µM; 10 and 8 Gy = positive controls. (C) Change in micronucleated reticulocytes (MN-Ret) before (−) and 48 h after (+) whole body γ-irradiation with a dose of 2 Gy in Samhd1^+/+ (n = 8) and Samhd1^Δ/Δ (n = 5) mice. Fold change compared with the mean of Samhd1^+/+ before irradiation is shown (one-way ANOVA followed by Tukey’s multiple comparison test). (D) Relative change in MN-NCEs from peripheral blood of mice with the indicated genotypes. Fold change was calculated for each genetic background between Samhd1^+/+ (+) and Samhd1^Δ/Δ (Δ). For Mavs and Sting1: + = WT/WT, − = KO/KO, n ≥ 4 for each group (Student’s t test). * = P < 0.05, *** = P < 0.001, **** = P < 0.0001.