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The Ngal reporter mouse detects the response of the kidney to injury in real time
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Journal Article
The Ngal reporter mouse detects the response of the kidney to injury in real time
2011
Overview
The current diagnosis of acute kidney injury involves the measurement of renal biomarkers, such as serum creatinine, which provide a crude means of detecting cellular stress and injury. To determine whether Ngal expression provides an alternate renal biomarker capable of detecting the initial phases of renal injury, Paragas
et al
. have developed an Ngal reporter mouse that offers a noninvasive and real-time method for the continuous and quantitative reporting of cell stress and injury at the injury site.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 692/53
/ Acute-Phase Proteins - genetics
/ Acute-Phase Proteins - physiology
/ Animals
/ Biomedical and Life Sciences
/ Dose-Response Relationship, Drug
/ Female
/ Gene Expression Regulation - genetics
/ Gene Expression Regulation - physiology
/ Genes
/ Genes, Reporter - drug effects
/ Genes, Reporter - physiology
/ Injuries
/ Kidneys
/ Male
/ Mice
/ Mice, Mutant Strains - genetics
/ Mice, Mutant Strains - physiology
/ Oncogene Proteins - genetics
/ Oncogene Proteins - physiology
/ Proteins
/ Rodents
