title: The β2-adrenergic receptor as a surrogate odorant receptor in mouse olfactory sensory neurons.
abstract: In the mouse, mature olfactory sensory neurons (OSNs) express one allele of one of the ~1200 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express the same OR coalesce into homogeneous glomeruli at conserved positions in the olfactory bulb. ORs are involved in OR gene choice and OSN axonal wiring, but the mechanisms remain poorly understood. One approach is to substitute an OR genetically with another GPCR, and to determine in which aspects this GPCR can serve as a surrogate OR under experimental conditions. Here, we characterize a novel gene-targeted mouse strain in which the mouse β2-adrenergic receptor (β2AR) is coexpressed with tauGFP in OSNs that choose the OR locus M71 for expression (β2AR→M71-GFP). By crossing these mice with β2AR→M71-lacZ gene-targeted mice, we find that differentially tagged β2AR→M71 alleles are expressed monoallelically. The OR coding sequence is thus not required for monoallelic expression - the expression of one of the two alleles of a given OR gene in an OSN. We detect strong β2AR immunoreactivity in dendritic cilia of β2AR→M71-GFP OSNs. These OSNs respond to the β2AR agonist isoproterenol in a dose-dependent manner. Axons of β2AR→M71-GFP OSNs coalesce into homogeneous glomeruli, and β2AR immunoreactivity is detectable within these glomeruli. We do not find evidence for expression of endogenous β2AR in OSNs of wild-type mice, also not in M71-expressing OSNs, and we do not observe overt differences in the olfactory system of β2AR and β1AR knockout mice. Our findings corroborate the experimental value of the β2AR as a surrogate OR, including for the study of the mechanisms of monoallelic expression.
authors.affiliation: Max Planck Research Unit for Neurogenetics, Max-von-Laue-Strasse 3, 60438 Frankfurt, Germany.
authors.forename: Masayo
authors.initials: M
authors.lastname: Omura
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Grosmaitre
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Minghong
authors.initials: M
authors.lastname: Ma
authors.affiliation: Max Planck Research Unit for Neurogenetics, Max-von-Laue-Strasse 3, 60438 Frankfurt, Germany. Electronic address: peter.mombaerts@biophys.mpg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Mombaerts
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D018035:Receptors, Odorant; D007545:Isoproterenol
keywords: G-protein coupled receptor; Main olfactory epithelium; Odorant receptor; β2-adrenergic receptor