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

Mol Cell Biol. 2000 Jun;20(11):4106-14. doi: 10.1128/MCB.20.11.4106-4114.2000.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1
  • Gene Expression
  • Gene Targeting
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Mutagenesis, Insertional
  • Phenotype
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology*
  • Receptors, HIV / genetics
  • Receptors, HIV / physiology*

Substances

  • CX3C Chemokine Receptor 1
  • Luminescent Proteins
  • Receptors, Cytokine
  • Receptors, HIV
  • Green Fluorescent Proteins