The Ngal reporter mouse detects the response of the kidney to injury in real time.

The Ngal reporter mouse detects the response of the kidney to injury in real time.
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DOI:
10.1038/nm.2290
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发表时间:
2011-02
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
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许多蛋白质已被提出作为器官损伤的替代标志物,但对于许多候选者,将蛋白质与受损器官联系起来的基本特征尚未被描述。我们通过将双融合报告基因Luciferase 2(Luc 2)/mCherry(mC)插入Ngal基因座来产生NGAL报告基因小鼠。Ngal-Luc 2/mC报告基因准确地再现了内源性信息,并实时阐明了体内损伤。在肾脏中,Ngal-Luc 2/mC成像显示出与肾小管应激的灵敏、快速、剂量依赖性、可逆和器官和细胞特异性关系,其定量测定尿Ngal(uNgal)。出乎意料的是,远端肾单位的特定细胞是uNgal的来源。从Ngal-Luc 2/mC小鼠中分离的细胞也可以跟踪损伤的发生和消退,并在感染的情况下监测NF-κB抑制剂和抗生素的作用。因此,Ngal-Luc 2/mC小鼠和细胞的成像鉴定了影响肾损伤的损伤剂和修复剂。
Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential characteristics which link the protein to the injured organ have not yet been described. We generated an NGAL-reporter mouse by inserting a di-fusion reporter gene, Luciferase2(Luc2)/mCherry(mC) into the Ngal 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 cellular specific relationship with tubular stress, which quantitatively paralleled urinary Ngal (uNgal). Unexpectedly, specific cells of the distal nephron were the source of uNgal. Cells isolated from Ngal-Luc2/mC mice could also track both the onset and the resolution of the injury, and monitor the actions of NF-κB inhibitors and antibiotics in the case of infection. Accordingly, the imaging of Ngal-Luc2/mC mice and cells identified injurious and reparative agents which effect kidney damage.
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