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The Journal of Neuroscience, July 1, 2001, 21(13):4637-4648

The OMP-lacZ Transgene Mimics the Unusual Expression Pattern of OR-Z6, a New Odorant Receptor Gene on Mouse Chromosome 6: Implication for Locus-Dependent Gene Expression

Martina Pyrski¹, Zheng Xu¹, Eric Walters², Debra J. Gilbert³, Nancy A. Jenkins³, Neal G. Copeland³, and Frank L. Margolis¹

¹ Department of Anatomy and Neurobiology, School of Medicine, University of Maryland at Baltimore, Baltimore, Maryland 21201, ² Department of Biochemistry and Molecular Biology, Howard University Medical College, Washington, DC 20059, and ³ Mouse Cancer Genetics Program, National Cancer Institute-Frederick, Frederick, Maryland 21702

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 locus-dependent mechanisms.

Key words: transgene; receptors; OR-Z6; olfactory neurons; olfactory epithelium; olfactory bulb; expression patterns; in situ hybridization; locus dependence; OMP promoter

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21134637-12$05.00/0

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