Fig. 7: Discn knockout (KO) in mice induces massive DNA DSBs and immune reaction.

Discn KO mouse brains contained higher level of DNA DSBs than WT counterparts, as indicated by γH2AX staining (a) and comet assay (b). SVZ, subventricular zone. KO (+/− × +/−) indicated the KO mice were from Discn^+/− crossing, whereas KO (−/− × −/−) indicated the KO mice were from Discn^−/− crossing. Scale bar, 100 μm. At least 100 tails were analyzed in each comet assay group in three independent replications. Data were representative of individual values with box and whiskers plots showing the median, upper and lower quartiles, and minimum and maximum. Two-tailed Student’s t-test. c Discn KO mouse brains contained higher level of cytosolic dsDNA than WT mice. Mice were 1 day old in (a–c). d The STING pathway was activated in Discn KO mouse brains, as indicated by the phosphorylation of TBK1 and IRF3, as well as the induction of type 1 interferon expression. Three independent experiments were repeated with similar results. e The inflammasomes were activated in Discn KO mouse brains, as indicated by the detection of cleaved caspase 1 (c-CASP1) and mature IL-1β. Three independent experiments were repeated with similar results. f Heatmap of differential expressed genes (DEGs) between Discn KO and WT counterpart mice brains. g Gene ontology (GO) enrichments of DEGs shown in (f). Adult mice were used in (d–g).