title: Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems.
abstract: Formyl peptide receptor 3 (Fpr3, also known as Fpr-rs1) is a G protein-coupled receptor expressed in subsets of sensory neurons of the mouse vomeronasal organ, an olfactory substructure essential for social recognition. Fpr3 has been implicated in the sensing of infection-associated olfactory cues, but its expression pattern and function are incompletely understood. To facilitate visualization of Fpr3-expressing cells, we generated and validated two new anti-Fpr3 antibodies enabling us to analyze acute Fpr3 protein expression. Fpr3 is not only expressed in murine vomeronasal sensory neurons but also in bone marrow cells, the primary source for immune cell renewal, and in mature neutrophils. Consistent with the notion that Fpr3 functions as a pathogen sensor, Fpr3 expression in the immune system is up-regulated after stimulation with a bacterial endotoxin (lipopolysaccharide). These results strongly support a dual role for Fpr3 in both vomeronasal sensory neurons and immune cells. We also identify a large panel of mouse strains with severely altered expression and function of Fpr3, thus establishing the existence of natural Fpr3 knock-out strains. We attribute distinct Fpr3 expression in these strains to the presence or absence of a 12-nucleotide in-frame deletion (Fpr3Δ424-435). In vitro calcium imaging and immunofluorescence analyses demonstrate that the lack of four amino acids leads to an unstable, truncated, and non-functional receptor protein. The genome of at least 19 strains encodes a non-functional Fpr3 variant, whereas at least 13 other strains express an intact receptor. These results provide a foundation for understanding the in vivo function of Fpr3.
authors.affiliation: From the Center for Integrative Physiology and Molecular Medicine and.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Stempel
authors.affiliation: the Department of Biochemistry, Saarland University School of Medicine, 66421 Homburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.affiliation: From the Center for Integrative Physiology and Molecular Medicine and.
authors.forename: Anabel
authors.initials: A
authors.lastname: Pérez-Gómez
authors.affiliation: From the Center for Integrative Physiology and Molecular Medicine and.
authors.forename: Trese
authors.initials: T
authors.lastname: Leinders-Zufall
authors.affiliation: From the Center for Integrative Physiology and Molecular Medicine and.
authors.forename: Frank
authors.initials: F
authors.lastname: Zufall
authors.affiliation: From the Center for Integrative Physiology and Molecular Medicine and bernd.bufe@uks.eu.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bufe
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000276:immunology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000276:immunology*; D013045:Species Specificity; D019147:Vomeronasal Organ / Q000166:cytology / Q000276:immunology*
chemical_list: D044042:Receptors, Formyl Peptide
keywords: G protein-coupled receptor; cellular immune response; chemotaxis; gene expression; genetic polymorphism; immunodeficiency; neuroimmunology; olfaction; olfactory receptor (OR); pattern recognition receptor (PRR)