This targeted substitution of the beta 2 adrenergic receptor (Adbr2) in place of olfactory receptor 151 (Olfr151, also known as M71) drives expression of this non-olfactory G-protein coupled receptor in a pattern consistent with normal Olfr151 expression as assessed by the bicistronically expressed tauGFP marker. At three weeks of age an average of 1,262 cells in the dorsal main olfactory epithelium express GFP in homozygotes. Co-staining for OMP and GAP43 shows that these olfactory sensory neurons are, as a population, somewhat less mature than wild-type Olfr151-expressing olfactory sensory neurons. These Adbr2-expressing olfactory sensory neurons respond in a dose-dependent manner to isoproterenol, but not to acetophenone, a ligand for Olfr151. Wholemount immunohistochemistry shows that Adbr2 protein localizes in the dendritic cilia of the olfactory sensory neurons, similar to localization of olfactory receptor proteins. When crossed with Olfr151tm26Mom homozygotes, which have an IRES-taulacZ insertion bicistronically expressed downstream of the endogenous Olfr151 coding sequence (see stock 006676) the compound heterozygous offspring show no double-positive cells. This monoallelic expression proves that allelic exclusion of olfactory receptors does not require the endogenous olfactory receptor protein or DNA sequence. Expression of olfactory receptors and Adbr2 in the main olfactory epithelium, assessed by in situ hybridization, strongly suggests that olfactory sensory neurons that express Adbr2 do not co-express an olfactory receptor, so this substitution permits Adbr2 to function in place of an olfactory receptor with normal monogenic expression and allelic exclusion. In heterozygotes the axons of these Adbr2-expressing olfactory sensory neurons coalesce into homogeneous glomeruli distinct from M71 glomeruli. While there are approximately the same number of M71 glomeruli and Adbr2 glomeruli, the Adbr2 glomeruli are smaller, by approximately half. In compound heterozygotes expressing this allele and Olfr151tm14(Adrb2)Mom, which has the same Adbr2 substitution but with a taulacZ bicistronic marker (see stock 006691), the Adbr2 expressing axons coalesce into the same glomeruli.
