Molecular mechanisms regulating mono-allelic odorant receptor expression.

摘要

A family of odorant receptors (ORs) specifically expressed in the neurons of the olfactory epitheliuim are responsible for detecting odorous chemicals present in the environment. ORs also play a role in axon guidance in addition to their direct role in odor recognition. Each olfactory neuron selects a single odorant receptor (OR) allele for expression from a repertoire of more than 1000 OR genes. Mono-allelic OR expression establishes the functionally distinct neuronal populations required for odor discrimination and defines the axonal targets of individual olfactory neurons in the olfactory bulb. In this thesis, I identify a new role for OR protein as a critical component in a feedback mechanism that ensures the mono-allelic expression of OR genes. A second line of experiments reveal a defect in projections to the olfactory bulb in mice deficient for the O/E-3 transcription factor. Modification of the O/E binding sites present in OR promoters indicate that this projection phenotype may arise from an O/E-3-dependent alteration of OR expression. Additionally, a new technique for generating targeted transgenic mice using Flp recombinase based DNA integration was developed allowing future targeted OR expression constructs to be generated more efficiently.