TheOMP–lacZTransgene Mimics the Unusual Expression Pattern ofOR-Z6, a New Odorant Receptor Gene on Mouse Chromosome 6: Implication for Locus-Dependent Gene Expression

Abstract

Reporter gene expression in the olfactory epithelium of H-lacZ6 transgenic mice mimics the cell-selective expression pattern known for some odorant receptor genes. The transgene construct in these mice consists of the lacZ coding region, driven by the proximal olfactory marker protein (OMP) gene promoter, and shows expression in a zonally confined subpopulation of olfactory neurons. To address mechanisms underlying the odorant receptor-like expression pattern of the lacZ construct, we analyzed the transgene-flanking region and identified OR-Z6, the first cloned odorant receptor gene that maps to mouse chromosome 6. OR-Z6 bears the highest sequence similarity (85%) to a human odorant receptor gene at the syntenic location on human chromosome 7. We analyzed the expression pattern of OR-Z6 in olfactory tissues of H-lacZ6 mice and show that it bears strong similarities to that mapped for ␤-galactosidase. Expression of both genes in olfactory neurons is primarily restricted to the same medial subregion of the olfactory epithelium. Axons from both neuronal subpopulations project to the same ventromedial aspect of the anterior olfactory bulbs. Furthermore, colocalization analyses in H-lacZ6 mice demonstrate that OR-Z6-reactive glomeruli receive axonal input from lacZ-positive neurons as well. These results suggest that the expression of both genes is coordinated and that transgene expression in H-lacZ6 mice is regulated by locusdependent mechanisms.

OMP Gene Deletion Results in an Alteration in Odorant-Induced Mucosal Activity Patterns

“…4, raw responses, and 6, differential odorant pattern responses) are far from homogeneous. This lack of homogeneity in responsivity was consistent with the observations of several molecular studies that some receptor types (e.g., OR37 and OR-Z6) have a clustered distribution Kubick et al 1997;Pyrski et al 2001;Strotmann et al 1994) and that odorant receptors previously held to be randomly distributed within a given zone are instead distributed heterogeneously with an aggregation of receptors in a particular region (C. L. Iwema, H. Fang, D. B. Kurtz, S. L. Youngentob, and J. E. Schwob, unpublished results).…”

High-throughput microarray detection of olfactory receptor gene expression in the mouse

“…To validate the zonal results from the array experiments, we collected 31 OR genes represented on the array whose zonal distribution had been previously studied (30)(31)(32)(33)(34)(35). We were able to classify zones for 17 of these, and all but one were consistent with previous results.…”

“…However, this spatial expression pattern has been determined for fewer than 40 OR genes by in situ investigation (30)(31)(32)(33)(34)(35). This approach is far too labor intensive (and costly) to perform for each of the Ͼ1,000 genes, but the MOR array provides an effective tool for investigating this zonal pattern globally.…”

Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

“…probes for OR14, OR18, and OR133 indicate that the territory in which cross-hybridizing ORs are expressed is coextensive with that occupied by the reference OR, which has also been shown for the OR37 subfamily of ORs (Kubick et al, 1997;Strotmann et al, 1999;Pyrski et al, 2001). Given that coding sequence-containing probes hybridize to a detectable level only with ORs that share substantial sequence identity, it seems likely that members of the same OR subfamilies generally share the same territory, which was an interpretation offered previously (Vassar et al, 1993).…”

“…Individual OSNs express only one allele at a single OR locus at a high level (Chess et al, 1994). Furthermore, those neurons that express a particular OR are segregated to a limited region of the epithelium, conventionally asserted to correspond to one of three or four nonoverlapping zones, although the OR37 subfamily and other closely related ORs are obvious exceptions to that conventional formulation (Strotmann et al, 1992(Strotmann et al, , 1994a(Strotmann et al, ,b, 1999Ressler et al, 1993;Vassar et al, 1993;Kubick et al, 1997;Konzelmann et al, 1998;Pyrski et al, 2001). Finally, the axons of all of the OSNs that express a particular OR converge to a limited number of glomeruli generally found in only one locus in the medial glomerular layer and another in the lateral part (Ressler et al, 1994;Vassar et al, 1994;Mombaerts et al, 1996;Wang et al, 1998).…”