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

Item Type:Article
Title:The Ngal reporter mouse detects the response of the kidney to injury in real time
Creators Name:Paragas, N. and Qiu, A. and Zhang, Q. and Samstein, B. and Deng, S.X. and Schmidt-Ott, K.M. and Viltard, M. and Yu, W. and Forster, C.S. and Gong, G. and Liu, Y. and Kulkarni, R. and Mori, K. and Kalandadze, A. and Ratner, A.J. and Devarajan, P. and Landry, D.W. and D'Agati, V. and Lin, C.S. and Barasch, J.
Abstract: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.
Keywords:Acute-Phase Proteins, Biological Markers, Cisplatin, Drug Dose-Response Relationship, Gene Expression Regulation, Gentamicins, Kidney, Lipid A, Lipocalins, Mutant Strains Mice, Oncogene Proteins, Reporter Genes, Animals, Mice
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:216-222
Date:February 2011
Official Publication:https://doi.org/10.1038/nm.2290
PubMed:View item in PubMed

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