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. 2022 Mar 30;5:287. doi: 10.1038/s42003-022-03241-y

Fig. 4. Loss of necroptosis regulators in naked mole-rats (NMRs).

Fig. 4

a Venn diagram showing the number of genes upregulated in both mouse and NMR skin upon lipopolysaccharide (LPS) treatment; genes upregulated specifically in mouse or NMR skin upon exposure to 3-methylcholanthrene (3MC, 1 week) and UV; and enriched pathways of 3MC-UV Mouse-DEGs. b Multiple alignments of receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) sequences from the NMR, Damaraland mole-rat (DMR), guinea pig (GP), rat, human, and mouse. Frame-shift mutations and premature stop codons in the NMR sequence are boxed. Reading frames for the NMR and mouse sequences are indicated. The functional domains are shown above the alignments. c Cell death analysis in fibroblasts treated with a combination of TNF-α (T), cycloheximide (C), z-VAD-fmk (Z), or Nec-1 (N). Data are presented as the mean ± SD of n = 3 independent experiments. d Immunofluorescence staining of high mobility group box-1 protein (HMGB1) in skin at 1 week after 3MC-injection. Scale bar: 10 μm. e Quantification of cytoplasmic HMGB1 in skin after each treatment. Data are presented as the mean ± SD of n = 3 animals for each species. One-way ANOVA with Tukey’s multiple comparison test for (c) and Dunnett’s multiple comparisons test versus untreated control (Ctrl) for (e).