The beta 2-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 similar to 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 beta 2-adrenergic receptor (beta 2AR) is coexpressed with tauGFP in OSNs that choose the OR locus M71 for expression (beta 2AR -> M71-GFP). By crossing these mice with beta 2AR -> M71-lacZ gene-targeted mice, we find that differentially tagged beta 2AR -> 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 (beta 2AR immunoreactivity in dendritic cilia of (beta 2AR -> M71-GFP OSNs. These OSNs respond to the beta 2AR agonist isoproterenol in a dose-dependent manner. Axons of beta 2AR -> M71-GFP OSNs coalesce into homogeneous glomeruli, and beta 2AR immunoreactivity is detectable within these glomeruli. We do not find evidence for expression of endogenous beta 2AR in OSNs of wild-type mice, also not in M71-expressing OSNs, and we do not observe overt differences in the olfactory system of beta 2AR and beta 1AR knockout mice. Our findings corroborate the experimental value of the beta 2AR as a surrogate OR, including for the study of the mechanisms of monoallelic expression. (C) 2013 Elsevier Inc All rights reserved