Characterization of cDNA and genomic sequences encoding a canine chemokine receptor, CXCR4 and its ligand CXCL12.

The interaction of chemokine receptor CXCR4 and its functional ligand CXCL12 plays a key role in bone marrow hematopoiesis, neuronal and cardiovascular development, and organization of the immune system. Despite the importance of the CXCL12-CXCR4 axis for regulating hematopoiesis, information on the canine CXCR4 and CXCL12 genes is insufficient. In this present study, we identified the canine counterparts of the CXCR4 and CXCL12 cDNAs and genes. The amino acid sequence encoding canine CXCR4 showed the structural characteristics of seven transmembrane domain G protein-coupled receptors and high homology with those of humans and other animals. Two isoforms, CXCL12 alpha and CXCL12 beta, were identified in dogs, as described in human and other animals. The gene structures for canine CXCR4 and CXCL12 were similar to those of other animals. The canine CXCL12 gene structure indicated that the transcripts of the isoforms arose from alternative mRNA splicing. A single nucleotide polymorphism (SNP) with synonymous substitution was observed in the exon of the canine CXCL12 gene. mRNAs encoding canine CXCR4 and CXCL12 were expressed widely and constitutively. Molecular homology and constitutive expression of CXCR4 and CXCL12 mRNAs in canine normal tissues suggests critical roles in hematopoiesis and trafficking of leukocytes, as shown in other animals.