Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
J Vet Med Sci. 2024 Nov 1;86(11):1124-1128. doi: 10.1292/jvms.23-0344. Epub 2024 Sep 18.
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, CadDNase1L3DNase1, 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.
无细胞游离 DNA（cfDNA）是血液循环中的 DNA，是诊断遗传性疾病和肿瘤的有用标志物。然而，cfDNA 产生的机制尚不完全清楚。我们之前研究了核酸内切酶[半胱天冬氨酸蛋白酶激活的核酸内切酶（CAD）、DNase1L3 和 DNase I]，并报告在对乙酰氨基酚诱导的肝坏死中，DNase1L3 是产生 cfDNA 的主要内切核酸酶，CAD 起辅助作用。在这项研究中，我们生成了三基因敲除（TKO）小鼠 CadDNase1L3DNase1，并发现 DNase I 也有助于 cfDNA 的产生。鉴于 DNase1L3 或 DNase I 的缺陷与自身免疫性疾病有关，TKO 小鼠可用作疾病模型，并有助于鉴定内切核酸酶在体内的作用。
