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通过在转基因小鼠体内生物发光成像技术追踪 Nfκb2 基因在炎症过程中的动态表达。

Tracing the dynamic expression of the Nfκb2 gene during inflammatory processes by in vivo bioluminescence imaging in transgenic mice.

机构信息

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Engineering Research Center for Model Organisms, SRCMO/SMOC, Shanghai, 201203, China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 18;501(1):41-47. doi: 10.1016/j.bbrc.2018.04.126. Epub 2018 Apr 27.

Abstract

Nfκb2(p52/p100) plays essential roles in many chronic inflammatory diseases. Tracing the dynamic expression of Nfκb2 during different biological processes in vivo can provide valuable clues to understand the biological functions of this gene and develop anti-inflammatory drugs. In this study, B6-Tg(Nfκb2-luc) transgenic mouse line, a mouse model in which the expression of firefly luciferase gene is under the control of a 14.6-kb mouse Nfκb2 promoter, was generated to monitor the expression of p52/p100 in vivo. Bioluminescence imaging was used for tracking the luciferase signal in living mice in a variety of inflammatory processes, including LPS-induced sepsis and inflammatory bowel disease (IBD). The data of in vivo bioluminescence imaging in this mouse model showed that luciferase activity coincided with the endogenous p52/p100 expression. Moreover, dexamethasone or aspirin, two routine anti-inflammatory drugs, could decrease the high-level expression of luciferase induced by LPS. Overall, our results suggest that the B6-Tg(Nfκb2-luc) mice represent a valuable reporter mouse model not only to monitor the expression of p52/p100 in physiological or pathological processes but also to evaluate the effects of various anti-inflammatory drug treatments in vivo.

摘要

NF-κB2(p52/p100) 在许多慢性炎症性疾病中发挥着重要作用。追踪 NF-κB2 在体内不同生物学过程中的动态表达,可以为理解该基因的生物学功能和开发抗炎药物提供有价值的线索。在这项研究中,我们构建了 B6-Tg(Nfκb2-luc) 转基因小鼠品系,该小鼠模型中萤火虫荧光素酶基因的表达受 14.6kb 大小的小鼠 NF-κB2 启动子的控制,用于监测 p52/p100 在体内的表达。生物发光成像技术被用于追踪活体小鼠中荧光素酶信号,以跟踪多种炎症过程,包括 LPS 诱导的败血症和炎症性肠病 (IBD)。该小鼠模型的体内生物发光成像数据表明,荧光素酶活性与内源性 p52/p100 表达一致。此外,地塞米松或阿司匹林这两种常规抗炎药物可以降低 LPS 诱导的高荧光素酶表达水平。总之,我们的结果表明,B6-Tg(Nfκb2-luc) 小鼠不仅是一种监测生理或病理过程中 p52/p100 表达的有价值的报告小鼠模型,而且还可以评估各种抗炎药物在体内的治疗效果。

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