The Ngal reporter mouse detects the response of the kidney to injury in real time.
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.
College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Neal
N
Paragas
Andong
A
Qiu
Qingyin
Q
Zhang
Benjamin
B
Samstein
Shi-Xian
SX
Deng
Kai M
KM
Schmidt-Ott
Melanie
M
Viltard
Wenqiang
W
Yu
Catherine S
CS
Forster
Gangli
G
Gong
Yidong
Y
Liu
Ritwij
R
Kulkarni
Kiyoshi
K
Mori
Avtandil
A
Kalandadze
Adam J
AJ
Ratner
Prasad
P
Devarajan
Donald W
DW
Landry
Vivette
V
D'Agati
Chyuan-Sheng
CS
Lin
Jonathan
J
Barasch
D000209:Acute-Phase Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D017930:Genes, Reporter / Q000187:drug effects / Q000502:physiology*; D005839:Gentamicins / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008050:Lipid A / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics / Q000502:physiology; D015513:Oncogene Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D005839:Gentamicins; D008050:Lipid A; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D002945:Cisplatin
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