The seven-transmembrane receptor CX(3)CR1 is a specific receptor for the novel CX(3)C
chemokine fractalkine (FKN) (neurotactin). In vitro data suggest that membrane anchoring
of FKN, and the existence of a shed, soluble FKN isoform allow for both adhesive and
chemoattractive properties. Expression on activated endothelium and neurons defines
FKN as a potential target for therapeutic intervention in inflammatory conditions,
particularly central nervous system diseases. To investigate the physiological function
of CX(3)CR1-FKN interactions, we generated a mouse strain in which the CX(3)CR1 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 assign murine CX(3)CR1
expression to monocytes, subsets of NK and dendritic cells, and the brain microglia.
Analysis of CX(3)CR1-deficient mice indicates that CX(3)CR1 is the only murine FKN
receptor. Yet, defying anticipated FKN functions, absence of CX(3)CR1 interferes neither
with monocyte extravasation in a peritonitis model nor with DC migration and differentiation
in response to microbial antigens or contact sensitizers. Furthermore, a prominent
response of CX(3)CR1-deficient microglia to peripheral nerve injury indicates unimpaired
neuronal-glial cross talk in the absence of CX(3)CR1.