College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Nat Med. 2011 Feb;17(2):216-22. doi: 10.1038/nm.2290. Epub 2011 Jan 16.
Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarker characteristics that link the protein to the injured organ have not yet been described. We generated an Ngal reporter mouse by inserting a double-fusion reporter gene encoding luciferase-2 and mCherry (Luc2-mC) into the Ngal (Lcn2) locus. The Ngal-Luc2-mC reporter accurately recapitulated the endogenous message and illuminated injuries in vivo in real time. In the kidney, Ngal-Luc2-mC imaging showed a sensitive, rapid, dose-dependent, reversible, and organ- and cell-specific relationship with tubular stress, which correlated with the level of urinary Ngal (uNgal). Unexpectedly, specific cells of the distal nephron were the source of uNgal. Cells isolated from Ngal-Luc2-mC mice also revealed both the onset and the resolution of the injury, and the actions of NF-κB inhibitors and antibiotics during infection. Thus, imaging of Ngal-Luc2-mC mice and cells identified injurious and reparative agents that affect kidney damage.
许多蛋白质被提议作为器官损伤的替代标志物，但对于许多候选标志物，将蛋白质与受损器官联系起来的基本生物标志物特征尚未描述。我们通过将编码荧光素酶-2 和 mCherry（Luc2-mC）的双融合报告基因插入 Ngal（Lcn2）基因座，生成了一种 Ngal 报告小鼠。Ngal-Luc2-mC 报告准确地重现了内源性信息，并实时照亮体内的损伤。在肾脏中，Ngal-Luc2-mC 成像显示出与管状应激的敏感、快速、剂量依赖性、可逆和器官及细胞特异性关系，与尿 Ngal（uNgal）水平相关。出乎意料的是，远端肾单位的特定细胞是 uNgal 的来源。从 Ngal-Luc2-mC 小鼠分离的细胞也揭示了损伤的发生和消退，以及在感染过程中 NF-κB 抑制剂和抗生素的作用。因此，Ngal-Luc2-mC 小鼠和细胞的成像确定了影响肾脏损伤的损伤性和修复性药物。
