Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion

The seven-transmembrane receptor CX(3)CR1 is a specific receptor for the no vel CX3C chemokine fractalkine (FKN) (neurotactin). In vitro data suggest t hat membrane anchoring of FKN, and the existence of a shed, soluble FKN iso form allow for both adhesive and chemoattractive properties. Expression on activated endothelium and neurons defines FKN as a potential target for the rapeutic intervention in inflammatory conditions, particularly central nerv ous system diseases. To investigate the physiological function of CX(3)CR1- FKN interactions, we generated a mouse strain in which the CX,CRI gene was replaced by a green fluorescent protein (GFP) reporter gene. In addition to the creation of a mutant CX(3)CR1 locus, this approach enabled us to assig n murine CX(3)CR1 expression to monocytes, subsets of NK and dendritic cell s, and the brain microglia. Analysis of CX(3)CR1-deficient mice indicates t hat CX(3)CR1 is the only murine FKN receptor. Yet, defying anticipated FKN functions, absence of CX(3)CR1 interferes neither with monocyte extravasati on in a peritonitis model nor with DC migration and differentiation in resp onse to microbial antigens or contact sensitizers. Furthermore, a prominent response of CX(3)CR1-deficient microglia to peripheral nerve injury indica tes unimpaired neuronal-glial cross talk in the absence of CX(3)CR1.