The overall aim of the application is to determine the mechanism by which a single olfactory receptor is expressed in an olfactory neuron. It is suggested that there may be cis-stochastic mechanisms by which a single receptor gene is chosen to be expressed from a large linked array. The investigator proposes to generate transgenic mice carrying large YACs containing olfactory receptors and associated genomic sequences. The olfactory receptor is modified by the addition of a tau-lacZ marker preceded by an internal ribosomal entry site sequence so that expression of the receptor can be followed. The investigator has already demonstrated that such a 300 kb YAC containing the olfactory receptor M12 appears to replicate the expression pattern of the endogenous receptor to a large extent. The goal of the first aim is to create truncated versions of this M12- containing YAC to further delineate the site(s) required for regulation. Transgenic mice will be generated carrying truncated versions of the YAC and expression patterns will be examined. This is expanded upon in the second aim to identify such sequence associated with other olfactory receptors, and to determine if similar mechanisms and sequences are used. It is known that only a single allele of a receptor is expressed in a given cell. The choice of allele is random. In the third aim, the investigator proposes to use the transgenic mice generated in the inactivation and, if so, also determine if there is a site mediating this inactivation (much like Xist).
| Ebrahimi, F A; Edmondson, J; Rothstein, R et al. (2000) YAC transgene-mediated olfactory receptor gene choice. Dev Dyn 217:225-31 |
| Ebrahimi, F A; Chess, A (2000) Olfactory neurons are interdependent in maintaining axonal projections. Curr Biol 10:219-22 |
