Effects of nucleases on cell-free extrachromosomal circular DNA (Mus musculus). Mus musculus

In this study, we aimed to explore the relationship between nucleases and eccDNA characteristics in plasma. By using knockout mouse models with deficiencies in deoxyribonuclease 1 (DNASE1) or deoxyribonuclease 1 like 3 (DNASE1L3), we found that cell-free eccDNA in Dnase1l3 knockout mice exhibited larger size distributions than that in wild-type mice. Such size alterations were not found in tissue eccDNA of either Dnase1knockout or Dnase1l3 knockout mice, suggesting that DNASE1L3 could digest eccDNA extracellularly but did not seem to affect intracellular eccDNA.

本研究旨在探究血浆中核酸酶与染色体外环状DNA（extrachromosomal circular DNA，简称eccDNA）特征之间的关联。通过构建脱氧核糖核酸酶1（DNASE1）或脱氧核糖核酸酶1样3（DNASE1L3）缺陷的基因敲除小鼠模型，我们发现，DNASE1L3基因敲除小鼠体内的无细胞eccDNA尺寸分布显著大于野生型小鼠。此类尺寸改变并未在Dnase1基因敲除或Dnase1l3基因敲除小鼠的组织eccDNA中被观测到，这提示DNASE1L3可在细胞外对eccDNA进行酶解，但似乎并不影响细胞内的eccDNA。