DIFFERENTIAL EXPANSION OF THE N-FORMYLPEPTIDE RECEPTOR GENE-CLUSTER IN HUMAN AND MOUSE

The humam formylpeptide receptor (FPR) gene cluster has three members: FPR1 and FPRL1, which are expressed in neutrophils and monocytes and encode seven-transmembrane-domain chemotactic receptors specific for N -formylpeptides, and FPRL2, whose function is unknown. The FPRL1 recep tor is also a lipoxin A4 receptor. Using probes for the three human ge nes we have cloned six distinct mouse genes, designated Fpr1 and Fpr-r s1 through Fpr-rs5 which form a cluster on chromosome 17 in a region o f conserved synteny with human chromosome 19. Fpr1 encodes a functiona l receptor and is clearly the orthologue of FPR1.. Both Fpr-rs1 and Fp r-rs2 have higher sequence homology to FPRL1 than to FPRL2; Fpr-rs1 is 97% identical in amino acid sequence to a previously reported cDNA th at encodes a lipoxin A4 receptor, whereas the putative ligand for Fpr- rs2 is unknown. Fpr-rs3, Fpr-rs4, and Fpr-rs5 appear to lack human cou nterparts and are most similar in sequence to FPRL1. RNA for Fpr1, Fpr -rs1, and Fpr-rs2 is present in leukocytes, spleen, and lung whereas R NA for Fpr-rs3 was detected only in skeletal muscle. We did not detect Fpr-rs4 or Fpr-rs5 RNA in any tissue tested. Moreover, Fpr-rs5 has a stop codon in the protein-coding region corresponding to transmembrane domain VI and may not encode a functional receptor. These results sug gest that the FPR gene cluster has undergone differential expansion in mammals with FPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4, and Fpr-rs5 arising af ter divergence of human and mouse. (C) 1998 Academic Press.