Development of transgenic mice overexpressing mouse carbonyl reductase 1
Development of transgenic mice overexpressing mouse carbonyl reductase 1
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DOI：
10.1007/s11033-022-07994-x
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发表时间：
2022-11-09
影响因子：
2.8
通讯作者：
Yokoayama，Yoshihito
中科院分区：
文献类型：
--
作者：
Yokoyama，Minako;Fujita，Toshitsugu;Yokoayama，Yoshihito
羰基还原酶1（CBR 1）是一种依赖于烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的还原酶，具有广泛的底物特异性。CBR 1催化许多羰基化合物的还原，包括醌类、甘草素、甲萘醌和多种外源性物质，同时还参与各种细胞过程，如致癌、凋亡、信号转导和耐药性。在这项研究中，我们的目的是产生转基因小鼠过表达小鼠CBR 1（mCbr 1），其特点是在不同的器官中的mCbr 1的表达，并确定蛋白质表达patterns.Methods和ResultsTo促进更深入地了解CBR 1的功能，我们产生的转基因小鼠过表达CBR 1在整个身体。这些转基因小鼠在CAG启动子下过表达3xFLAG标记的mCbr 1（3xFLAG-mCbr 1）。产生了两种转基因小鼠品系，一种在多个组织中具有3xFLAG-mCbr 1表达，另一种在心脏中具有3xFLAG-mCbr 1的特异性表达。使用转基因小鼠心脏的通路和网络分析鉴定了73种蛋白质，其表达水平与mCbr 1过表达相关。结论mCbr 1转基因小鼠可用于进一步研究Cbr 1调控的分子机制，为深入了解其在肿瘤发生中的作用及某些抗癌药物的心脏毒性提供理论依据。
BackgroundCarbonyl reductase 1 (CBR1) is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase with broad substrate specificity. CBR1 catalyzes the reduction of numerous carbonyl compounds, including quinones, prostaglandins, menadione, and multiple xenobiotics, while also participating in various cellular processes, such as carcinogenesis, apoptosis, signal transduction, and drug resistance. In this study, we aimed to generate transgenic mice overexpressing mouse Cbr1 (mCbr1), characterize the mCbr1 expression in different organs, and identify changes in protein expression patterns.Methods and ResultsTo facilitate a deeper understanding of the functions of CBR1, we generated transgenic mice overexpressing CBR1 throughout the body. These transgenic mice overexpress 3xFLAG-tagged mCbr1 (3xFLAG-mCbr1) under the CAG promoter. Two lines of transgenic mice were generated, one with 3xFLAG-mCbr1 expression in multiple tissues, and the other, with specific expression of 3xFLAG-mCbr1 in the heart. Pathway and network analysis using transgenic mouse hearts identified 73 proteins with levels of expression correlating with mCbr1 overexpression. The expression of voltage-gated anion channels, which may be directly related to calcium ion-related myocardial contraction, was also upregulated.ConclusionmCbr1 transgenic mice may be useful for further in vivo analyses of the molecular mechanisms regulated by Cbr1; such analyses will provide a better understanding of its effects on carcinogenesis and cardiotoxicity of certain cancer drugs.