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

被引：346

作者：

Paragas, Neal ^{[1
]}

Qiu, Andong ^{[1
]}

Zhang, Qingyin ^{[1
]}

Samstein, Benjamin ^{[1
]}

Deng, Shi-Xian ^{[1
]}

Schmidt-Ott, Kai M. ^{[2
]}

Viltard, Melanie ^{[1
]}

Yu, Wenqiang ^{[1
]}

Forster, Catherine S. ^{[1
]}

Gong, Gangli ^{[1
]}

Liu, Yidong ^{[1
]}

Kulkarni, Ritwij ^{[1
]}

Mori, Kiyoshi ^{[3
]}

Kalandadze, Avtandil ^{[1
]}

Ratner, Adam J. ^{[1
]}

Devarajan, Prasad ^{[4
]}

Landry, Donald W. ^{[1
]}

D'Agati, Vivette ^{[1
]}

Lin, Chyuan-Sheng ^{[1
]}

Barasch, Jonathan ^{[1
]}

机构：

[1] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA

[2] Max Delbruck Ctr Mol Med Berlin Buch, Berlin, Germany

[3] Kyoto Univ, Grad Sch Med, Kyoto, Japan

[4] Cincinnati Childrens Hosp, Cincinnati, OH USA

来源：

NATURE MEDICINE | 2011年 / 17卷 / 02期

关键词：

GELATINASE-ASSOCIATED LIPOCALIN; GLOMERULAR-FILTRATION-RATE; EARLY URINARY BIOMARKER; INNATE IMMUNE-RESPONSE; CARDIAC-SURGERY; ESCHERICHIA-COLI; EPITHELIAL-CELLS; SERUM CREATININE; RENAL INJURY; RAT-KIDNEY;

D O I：

10.1038/nm.2290

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-kappa B inhibitors and antibiotics during infection. Thus, imaging of Ngal-Luc2-mC mice and cells identified injurious and reparative agents that affect kidney damage.

引用

页码：216 / U113

页数：8

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