title: 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.
authors.affiliation: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Tiffany
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Ester
authors.initials: E
authors.lastname: Roffe
authors.forename: Joan M G
authors.initials: JM
authors.lastname: Sechler
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000378:metabolism; D007114:Immunization; D008070:Lipopolysaccharides / Q000008:administration & dosage; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013864:Thioglycolates / Q000008:administration & dosage; D019076:Transgenes / Q000235:genetics
chemical_list: C105101:FPR2 protein, human; C469993:Fpr-rs2 protein, mouse; C568901:Fpr-rs8 protein, mouse; D008070:Lipopolysaccharides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D013864:Thioglycolates