| First Author | Minshawi F | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 193 |
| PubMed ID | 30655563 | Mgi Jnum | J:275487 |
| Mgi Id | MGI:6304896 | Doi | 10.1038/s41598-018-36969-x |
| Citation | Minshawi F, et al. (2019) Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses. Sci Rep 9(1):193 |
| abstractText | 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-kappaB 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. |
