Anales RANF

S14-02 BAC TRANSGENIC MOUSE MODELS TO STUDY P2X7 EXPRESSION AND INTERACTIONS A. Nicke 1 , R. Kopp 1 , A. Ramírez-Fernández 1 , J. Hector 1 , Björn Rissiek 2 , Tobias Engel 3 1 Walter Straub Institute of Pharmacology and Toxicology, LMU Munich, Germany, 2 Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 3 Royal College of Surgeons in Ireland, Dublin, Ireland. The P2X7 receptor is expressed in immune cells and plays an important role in cytokine release. However, the investigation of its function in various other cell types has been challenged by its complex pharmacology and a lack of specific antibodies. Thus, important questions such as its cell-specific localisation, function, and protein interactions remain unclear. To address this issue, we generated a BAC transgenic mouse model in which an EGFP-tagged P2X7 receptor is overexpressed under the control of its BAC-derived endogenous promoter. We will describe the evaluation of this mouse model and compare the P2X7-EGFP expression with the EGFP expression in another BAC transgenic P2X7 reporter mouse (Tg(P2rx7 EGFP)FY174Gsat) in which a soluble EGFP is expressed. In addition, the P2X7R-EGFP mouse model is used to investigate the interaction and mutual interrelation of the P2X7 and P2X4 subtypes in native mouse tissue. Our data indicate substantial differences in the cell type-specific expression of soluble EGFP and the P2X7-EGFP fusion construct in the two BAC transgenic mouse models and provide evidence that the proposed P2X4-P2X7 interaction is of minor physiological relevance in native tissues. Possible reasons for the observed differences will be discussed. This Work is funded by the DFG (SFB 1328) and the European Union (Horizon 2020 Framework Programme No. 766124)