DNase I 在对乙酰氨基酚引起的肝损伤后 DNA 降解和游离 DNA 生成中的作用

IF 1.1 4区农林科学 Q3 VETERINARY SCIENCES Journal of Veterinary Medical Science Pub Date : 2024-11-01 Epub Date: 2024-09-18 DOI:10.1292/jvms.23-0344

Shuhei Takada, Shuhei Ogawa, Ryushin Mizuta

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引用次数: 0

摘要

无细胞 DNA（cfDNA）是血液循环中的 DNA，是诊断遗传性疾病和肿瘤的有效标志物。然而，cfDNA 的生成机制尚未完全明了。我们以前研究过 DNase [Caspase-activatedDNase（CAD）、DNase1L3 和 DNase I]，并报道在乙酰氨基酚诱导的肝坏死中，DNase1L3 是产生 cfDNA 的主要内切酶，CAD 起辅助作用。在这项研究中，我们产生了三基因敲除（TKO）小鼠，即Cad -/-DNase1L3 -/-DNase1 -/-，结果发现DNase I也参与了cfDNA的生成。鉴于DNase1L3或DNase I的缺陷与自身免疫性疾病有关，TKO小鼠可作为疾病模型和鉴定内切酶体内作用的工具。

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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.

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来源期刊

Journal of Veterinary Medical Science 农林科学-兽医学

CiteScore

2.30

自引率

8.30%

发文量

230

审稿时长

9-18 weeks

期刊介绍： JVMS is a peer-reviewed journal and publishes a variety of papers on veterinary science from basic research to applied science and clinical research. JVMS is published monthly and consists of twelve issues per year. Papers are from the areas of anatomy, physiology, pharmacology, toxicology, pathology, immunology, microbiology, virology, parasitology, internal medicine, surgery, clinical pathology, theriogenology, avian disease, public health, ethology, and laboratory animal science. Although JVMS has played a role in publishing the scientific achievements of Japanese researchers and clinicians for many years, it now also accepts papers submitted from all over the world.