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.

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We are grateful for the advice of Q. Al-Awqati and J.A. Oliver. This work was supported by a grant from the Office of Columbia University Technology Ventures. J.B., N.P. and A.Q. are supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (DK-55388 and DK-58872) and the March of Dimes for Birth Defects. Additional funding to J.B. was provided by the Glomerular Center of Columbia University.

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Author notes

    • Neal Paragas
    •  & Andong Qiu

    These authors contributed equally to this work.


  1. College of Physicians and Surgeons of Columbia University, New York, New York, USA.

    • Neal Paragas
    • , Andong Qiu
    • , Qingyin Zhang
    • , Benjamin Samstein
    • , Shi-Xian Deng
    • , Melanie Viltard
    • , Wenqiang Yu
    • , Catherine S Forster
    • , Gangli Gong
    • , Yidong Liu
    • , Ritwij Kulkarni
    • , Avtandil Kalandadze
    • , Adam J Ratner
    • , Donald W Landry
    • , Vivette D'Agati
    • , Chyuan-Sheng Lin
    •  & Jonathan Barasch
  2. Max-Delbruck Center for Molecular Medicine Berlin-Buch, Berlin, Germany.

    • Kai M Schmidt-Ott
  3. Kyoto University Graduate School of Medicine, Kyoto, Japan.

    • Kiyoshi Mori
  4. Cincinnati Children's Hospital, Cincinnati, Ohio, USA.

    • Prasad Devarajan


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N.P., A.Q. and C.-S.L. created the Ngal reporter mouse; Q.Z. and B.S. performed surgeries; S.-X.D., G.G., Y.L., D.W.L. created NF-κB inhibitors; N.P., R.K. and A.J.R. studied bacteria-induced Ngal expression; V.D. evaluated the pattern of Ngal expression; K.M.S.-O., M.V., W.Y., C.S.F., K.M., A.K. and P.D. analyzed data; N.P., A.Q. and J.B. and wrote the paper; A.Q., N.P. and J.B. invented the luminescent mouse.

Competing interests

Columbia University and Cincinnati Children's Hospital Medical Center have received licensing fees from Biosite (Inverness Medical) and Abbott Diagnostics.

Corresponding author

Correspondence to Jonathan Barasch.

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