Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses

Faisal Minshawi, Michael White, Werner Muller, Neil Humphreys, Dean Jackson, Barry J. Campbell, Antony Adamson, Stamatia Papoutsopoulou

Research output: Contribution to journalArticlepeer-review


Tumour necrosis factor (TNF) is a key cytokine during inflammatory responses and its dysregulation is detrimental in many inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Here, we used a bacterial artificial chromosome (BAC) construct that expresses luciferase under the control of the human TNF locus to generate a novel transgenic mouse, the hTNF.LucBAC strain. In vitro stimulation of hTNF.LucBAC cells of different origin revealed a cell specific response to stimuli demonstrating the integrated construct’s ability as a proxy for inflammatory gene response. Lipopolysaccharide was the most potent luciferase inducer in macrophages, while TNF was a strong activator in intestinal organoids. Lipopolysaccharide-induced luciferase activity in macrophages was downregulated by inhibitors of NF-B pathway, as well as by Interleukin-10, a known anti-inflammatory cytokine. Moreover, the transgene-dependent luciferase activity showed a positive correlation to the endogenous murine soluble TNF secreted to the culture medium. In conclusion, the hTNF.LucBAC strain is a valuable tool for studying and screening molecules that target TNF synthesis and will allow further functional studies of the regulatory elements of the TNF locus.
Original languageEnglish
JournalScientific Reports
Early online date17 Jan 2019
Publication statusPublished - 2019

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute


Dive into the research topics of 'Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses'. Together they form a unique fingerprint.

Cite this