Technology development: generation of a unique dual function P2X7 receptor knock-in/knock-out mouse enabling genetic-proteomic and functional analysis in health and disease

To generate a unique transgenic mouse that will be a game changer in targeting new treatments of human diseases, including arthritis, cancer, osteoporosis, multiple sclerosis, muscle degeneration, pain and psychiatric disorders. We have made key discoveries on the function of a signalling protein found on cells, which is called P2RX7. It is present in multiple organs (brain, bone, immune) and signals into the cell to control its death and proliferation – processes that must be balanced for maintaining a healthy body. A major impediment to current research on this key signalling molecule is the lack of means for switching it off selectively to identify its beneficial vs. detrimental functions. This project aims to overcome this obstacle by using a novel state-of-the-art genomic approach to develop a unique mouse model. For the first time, we will be able to stop P2RX7 function in any cell we chose and evaluate the consequences. This new technology, combined with the accomplishments of the applicants’ in this area, will establish Portsmouth at the centre of P2RX7 R&D for many years to come. Not only will this unique resource make us highly competitive for external funding, but it will also attract new academic and industrial partners and has potential for commercialization. To ensure confidentiality as well as comply with the now universal requirement by external funders for the proof-of-principle data, internal funding is the only mechanism by which we can to achieve this crucial competitive advantage. Subsequently, this model will be at the centre of large, multi-disciplinary grant applications to RCUK and H2020 - applicants already have in place a consortium of partners (see supporting letters) for grant proposals based on this model.