Characterization of Fpr-rs8, an atypical member of the mouse formyl peptide receptor gene family.

ABSTRACT

The formyl peptide receptor gene family encodes G protein-coupled receptors for phagocyte chemoattractants, including bacteria- and mitochondria-derived N-formylpeptides. The human family has 3 functional genes, whereas the mouse family has 7 functional genes and 2 possible pseudogenes (ΨFpr-rs2 and ΨFpr-rs3). Here we characterize ΨFpr-rs2, a duplication of Fpr-rs2. Compared to Fpr-rs2, the ΨFpr-rs2 ORF is 186 nucleotides shorter but 98% identical. Due to a deletion and frame shift, the sequences lack homology from amino acid 219-289. Both transcripts were detected constitutively in multiple immune organs; however, ΨFpr-rs2 was consistently less abundant than Fpr-rs2. LPS induced expression of ΨFpr-rs2, but not Fpr-rs2, in spleen and bone marrow. Both transcripts were detected constitutively in thioglycollate-elicited peritoneal neutrophils, whereas only Fpr-rs2 was detected in thioglycollate-elicited peritoneal macrophages. Both transcripts were induced in LPS-stimulated macrophages. ΨFpr-rs2-GFP fusion protein appeared in cytoplasm but not plasma membrane of transfected HEK 293 cells, whereas Fpr-rs2-GFP labeled only plasma membrane. Survival of ΨFpr-rs2(-/-) mice was 33% shorter than that of wild-type and heterozygous littermates (p < 0.05), but no signature pathology was identified. Since ΨFpr-rs2 is expressed in phagocytes and regulated by bacterial products, and may affect longevity, we propose renaming it Fpr-rs8, an atypical member of the formyl peptide receptor gene family.