Role of DNase I in DNA degradation and cell-free DNA generation after acetaminophen-induced hepatic injury

Cell-free DNA (cfDNA), the DNA in the blood circulation, is a useful marker for diagnosing hereditary diseases and tumors. However, the mechanisms underlying the generation of cfDNA are not completely understood. We previously studied DNases [Caspase-activated DNase (CAD), DNase1L3, and DNase I] and reported that in acetaminophen-induced liver necrosis, DNase1L3 was the main endonuclease generating cfDNA, with CAD playing a supporting role. In this study, we generated triple-gene knockout (TKO) mice, Cad^−/− DNase1L3^−/− DNase1^−/−, and found that DNase I also contributed to cfDNA generation. Given that a defect in DNase1L3 or DNase I is involved in autoimmune diseases, TKO mice would be useful as a disease model and tool for identifying the in vivo roles of endonucleases.