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At present, ACKR3 is considered a target for cancer and cardiovascular disorders, but less is known about the potential of ACKR3 as a target for brain disease. Further, mouse lines have been created to identify cells expressing the receptor, but there is no tool to visualize and study the receptor itself under physiological conditions. Here, we engineered a knock-in KI mouse expressing a functional ACKR3-Venus fusion protein to directly detect the receptor, particularly in the adult brain.
In HEK cells, native and fused receptors showed similar membrane expression, ligand induced trafficking and signaling profiles, indicating that the Venus fusion does not alter receptor signaling. We also found that ACKR3-Venus enables direct real-time monitoring of receptor trafficking using resonance energy transfer.
We fully mapped receptor expression across 14 peripheral organs and brain areas and found that ACKR3 is primarily localized to the vasculature in these tissues. In the periphery, receptor distribution aligns with previous reports. In conclusion, we have generated Ackr3-Venus knock-in mice with a traceable ACKR3 receptor, which will be a useful tool to the research community for interrogations about ACKR3 biology and related diseases.
G protein-coupled receptors GPCRs constitute the largest family of cell surface receptors. They are involved in a wide diversity of cellular and physiological processes and contribute to disease. Since this family of proteins are an essential component of the mechanisms regulating physio-pathological processes, it is necessary to have tools allowing their study in physiologically relevant systems.
