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Mutually exclusive expression of odorant receptor transgenes


To study the mutually exclusive expression of odorant receptor (OR) genes, we generated transgenic mice that carried the murine OR gene MOR28. Expression of the transgene and the endogenous MOR28 was distinguished by using two different markers, β-galactosidase and green fluorescent protein (GFP), respectively. Double staining of the olfactory epithelium revealed that the two genes were rarely expressed simultaneously in individual olfactory neurons. A similar exclusion was also observed between differently tagged but identical transgenes integrated into the same locus of one particular chromosome. Although allelic inactivation has been reported for the choice between the maternal and paternal alleles, this is the first demonstration of mutually exclusive activation among non-allelic OR gene members with identical coding and regulatory sequences. Such an unusual mode of gene expression, monoallelic and mutually exclusive, has previously been shown only for the antigen-receptor genes of the immune system.

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Figure 1: Expression of the transgenic MOR28 gene.
Figure 2: Structure of the transgenic YAC-460 region.
Figure 3: Detection of neurons expressing the transgenic and the GFP-tagged endogenous MOR28 genes.
Figure 4: Detection of OSNs expressing transgenic MOR28 genes.
Figure 5: Detection of glomeruli for MOR28-expressing neurons in coronal sections of the olfactory bulb.


  1. 1

    Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odorant recognition. Cell 65, 175–187 ( 1991).

    CAS  Article  Google Scholar 

  2. 2

    Parmentier, M. et al. Expression of members of the putative olfactory receptor gene family in mammalian germ cells. Nature 355, 453–455 (1992).

    CAS  Article  Google Scholar 

  3. 3

    Sullivan, S. L., Adamson, M. C., Ressler, K. J., Kozak, C. A. & Buck, L. B. The chromosomal distribution of mouse odorant receptor genes. Proc. Natl. Acad. Sci. USA 93, 884–888 (1996).

    CAS  Article  Google Scholar 

  4. 4

    Ben-Arie, N. et al. Olfactory receptor gene cluster on human chromosome 17: possible duplication of an ancestral receptor repertoire. Hum. Mol. Genet. 3, 229–235 ( 1994).

    CAS  Article  Google Scholar 

  5. 5

    Rouquier, S. et al. Distribution of olfactory receptor genes in the human genome . Nat. Genet. 18, 243–250 (1998).

    CAS  Article  Google Scholar 

  6. 6

    Ressler, K. J., Sullivan, S. L. & Buck, L. B. A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell 73, 597 –609 (1993).

    CAS  Article  Google Scholar 

  7. 7

    Vassar, R., Ngai, J. & Axel, R. Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74, 309– 318 (1993).

    CAS  Article  Google Scholar 

  8. 8

    Ngai, J. et al. Coding of olfactory information: topography of odorant receptor expression in the catfish olfactory epithelium. Cell 72, 667–680 (1993).

    CAS  Article  Google Scholar 

  9. 9

    Malnic, B., Hirono, J., Sato, T. & Buck, L. B. Combinatorial receptor codes for odors. Cell 96, 713– 723 (1999).

    CAS  Article  Google Scholar 

  10. 10

    Chess, A., Simon, I., Cedar, H. & Axel, R. Allelic inactivation regulates olfactory receptor gene expression. Cell 78, 823–834 (1994).

    CAS  Article  Google Scholar 

  11. 11

    Belluscio, L., Koentges, G., Axel, R. & Dulac, C. A map of pheromone receptor activation in the mammalian brain. Cell 97 , 209–220 (1999).

    CAS  Article  Google Scholar 

  12. 12

    Rodriguez, I., Feinstein, P. & Mombaerts, P. Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97, 199–208 (1999).

    CAS  Article  Google Scholar 

  13. 13

    Ressler, K. J., Sullivan, S. L. & Buck, L. B. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79, 1245–1255 ( 1994).

    CAS  Article  Google Scholar 

  14. 14

    Vassar, R. et al. Topographic organization of sensory projections to the olfactory bulb. Cell 79, 981–991 (1994).

    CAS  Article  Google Scholar 

  15. 15

    Mombaerts, P. et al. Visualizing an olfactory sensory map. Cell 87, 675–686 (1996).

    CAS  Article  Google Scholar 

  16. 16

    Wang, F., Nemes, A., Mendelsohn, M. & Axel, R. Odorant receptors govern the formation of a precise topographic map. Cell 93, 47–60 ( 1998).

    CAS  Article  Google Scholar 

  17. 17

    Tsuboi, A. et al. Olfactory neurons expressing closely linked and homologous odorant receptor genes tend to project their axons to neighboring glomeruli on the olfactory bulb. J. Neurosci. 19, 8409–8418 (1999).

    CAS  Article  Google Scholar 

  18. 18

    Qasba, P. & Reed, R. R. Tissue and zonal-specific expression of an olfactory receptor transgene. J. Neurosci. 18 , 227–236 (1998).

    CAS  Article  Google Scholar 

  19. 19

    Ebrahimi, F. A. W., Edmondson, J., Rothstein, R. & Chess, A. YAC transgene-mediated olfactory receptor gene choice. Dev. Dyn. 217, 225–231 ( 2000).

    CAS  Article  Google Scholar 

  20. 20

    Tonegawa, S. Somatic generation of antibody diversity. Nature 302 , 575–581 (1983).

    CAS  Article  Google Scholar 

  21. 21

    Strathern, J. N. et al. Homothallic switching of yeast mating type cassettes is initiated by a double-stranded cut in the MAT locus. Cell 31, 183–192 (1982).

    CAS  Article  Google Scholar 

  22. 22

    Borst, P. Molecular genetics and antigenic variation. Immunol. Today 12, 29–33 (1991).

    CAS  Article  Google Scholar 

  23. 23

    Krautwurst, D., Yau, K. W. & Reed, R. R. Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell 95 , 917–926 (1998).

    CAS  Article  Google Scholar 

  24. 24

    Callahan, C. A. & Thomas, J. B. Tau-beta-galactosidase, an axon-targeted fusion protein. Proc. Natl. Acad. Sci. USA 91, 5972–5976 (1994).

    CAS  Article  Google Scholar 

  25. 25

    Moriyoshi, K., Richards, L. J., Akazawa, C., O'Leary, D. D. M. & Nakanishi, S. Labeling neural cells using adenoviral gene transfer of membrane-targeted GFP. Neuron 16, 255–260 ( 1996).

    CAS  Article  Google Scholar 

  26. 26

    Gu, H., Zou, Y. R. & Rajewsky, K. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting . Cell 73, 1155–1164 (1993).

    CAS  Article  Google Scholar 

  27. 27

    Soriano, P., Montogomery, C., Geske, R. & Bradley, A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702 (1991).

    CAS  Article  Google Scholar 

  28. 28

    Yagi, T. et al. A novel negative selection for homologous recombination using diphtheria toxin A fragment gene. Anal. Biochem. 214 , 77–86 (1993).

    CAS  Article  Google Scholar 

  29. 29

    Bungert, J. et al. Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4. Genes Dev. 9, 3083–3096 (1995).

    CAS  Article  Google Scholar 

  30. 30

    Wutz, A. et al. Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389, 745– 749 (1997).

    CAS  Article  Google Scholar 

  31. 31

    Asano, M. et al. Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells. EMBO J. 16, 1850– 1857 (1997).

    CAS  Article  Google Scholar 

  32. 32

    Shibata, H. et al. Rapid colorectal adenoma formation inhibited by conditional targeting of the apc gene. Science 278, 120–123 (1997).

    CAS  Article  Google Scholar 

  33. 33

    Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl. Acad. Sci. USA 90, 8424–8428 ( 1993).

    CAS  Article  Google Scholar 

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We thank the following people for providing us with plasmid samples or cell lines: H. Gu (pGH-1), P. Soriano (pPGKneobpA), T. Yagi (DT-A cassette), J. Thomas (tau–lacZ cassette), K. Moriyoshi (pGAP–GFP), A. Nagy (R1 cells) and I. Saito (adenovirus vector). This work was supported by the Special Promotion Research Grants from the Ministry of Education and Culture of Japan and by grants from Toray Science Foundation, Nissan Science Foundation and Mitsubishi Foundation.

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Correspondence to Hitoshi Sakano.

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Serizawa, S., Ishii, T., Nakatani, H. et al. Mutually exclusive expression of odorant receptor transgenes. Nat Neurosci 3, 687–693 (2000).

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