Theranostics 2013; 3(11):841-850. doi:10.7150/thno.6997
Establishment of Stable Reporter Expression for In Vivo Imaging of Nuclear Factor-κB Activation in Mouse Liver
1. Beijing Institute of Transfusion Medicine, 27(9) TaiPing Road, Beijing, China;
2. In vivo Oncology and Pharmacology, Pharmaron, 6 Taihe Road, Beijing, China;
3. Department of Incretology, Navy General Hospital of PLA, Beijing, China.
* These authors contributed equally to this work.
The nuclear factor-κB (NF-κB) signaling pathway plays a critical role in a multitude of cellular processes. Activation of the NF-κB transcription factor family is essential for the initiation of inflammation, immunity, cell proliferation and apoptosis through a list of responsive genes. In hepatic tissue, activation of the NF-κB pathway has been implicated in a number of pathological conditions. Here we described a mouse model for noninvasive quantification of NF-κB activation in the hepatic tissues. Mice were subjected to hydrodynamic delivery with a mixture of pattB-NF-κB-Fluc reporter and φC31o integrase vector. Hepatic expression of φC31o integrase mediated chromosomal integration of the pattB-NF-κB-Fluc reporter, resulting in stable luciferase expression at 300 days post transfection. We applied noninvasive imaging and were able to detect NF-κB activation under acute liver injury and hepatitis conditions. During hepatectomy-induced liver regeneration, NF-κB activation was detected locally in the tissues at the surgery site. Treatment with Sorafenib suppressed NF-κB activation, accompanied with perturbation of liver regeneration. In conclusion, we established a method for stable transfection of the hepatic tissues and applied the transfected mice to longitudinal monitoring of NF-κB activity under pathological conditions. Further exploration of this methodology for establishment of other disease models and for evaluation of novel pharmaceuticals is likely to be fruitful.
Keywords: Nuclear factor-κB, noninvasive molecular imaging, φC31o integrase, Sorafenib, animal model.
Yan S, Fu Q, Zhou Y, Zhang N, Zhou Q, Wang X, Yuan Z, Wang X, Du J, Zhang J, Zhan L. Establishment of Stable Reporter Expression for In Vivo Imaging of Nuclear Factor-κB Activation in Mouse Liver. Theranostics 2013; 3(11):841-850. doi:10.7150/thno.6997. Available from http://www.thno.org/v03p0841.htm