Differential Expansion of the N-Formylpeptide Receptor Gene Cluster in Human and Mouse

The human formylpeptide receptor (FPR) gene cluster has three members:FPR1andFPRL1, which are expressed in neutrophils and monocytes and encode seven-transmembrane-domain chemotactic receptors specific for N-formylpeptides, andFPRL2,whose function is unknown. The FPRL1 receptor is also a lipoxin A4 receptor. Using probes for the three human genes we have cloned six distinct mouse genes, designatedFpr1andFpr-rs1throughFpr-rs5,which form a cluster on chromosome 17 in a region of conserved synteny with human chromosome 19.Fpr1encodes a functional receptor and is clearly the orthologue ofFPR1.BothFpr-rs1andFpr-rs2have higher sequence homology toFPRL1than toFPRL2; Fpr-rs1is 97% identical in amino acid sequence to a previously reported cDNA that encodes a lipoxin A4 receptor, whereas the putative ligand forFpr-rs2is unknown.Fpr-rs3, Fpr-rs4,andFpr-rs5appear to lack human counterparts and are most similar in sequence toFPRL1.RNA forFpr1, Fpr-rs1,andFpr-rs2is present in leukocytes, spleen, and lung, whereas RNA forFpr-rs3was detected only in skeletal muscle. We did not detectFpr-rs4orFpr-rs5RNA in any tissue tested. Moreover,Fpr-rs5has a stop codon in the protein-coding region corresponding to transmembrane domain VI and may not encode a functional receptor. These results suggest that the FPR gene cluster has undergone differential expansion in mammals withFPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4,andFpr-rs5arising after divergence of human and mouse.