The Olfr151 Odorant Receptor Gene is Resistant to Activation in Embryonic Stem Cells

A single allele of any of the ~1100 functional mouse odorant receptor (OR) genes is expressed by mature olfactory sensory neurons (mOSNs) through a poorly understood mechanism of singular gene choice. We were interested in developing an expression system to study OR selection in a mouse embryonic stem cell (mESC) carrying an Olfr151-IRES-CRE knock-in and a CRE-recombination-dependent ROSA26-MTMG reporter. Recombination of the ROSA reporter could not be observed after exposing this mESC to thousands of chemical compounds, including 175 compounds known to interfere with epigenetic regulatory processes nor by transfection with high probability Olfr151 promoter minigenes coexpressing CRE. The only two known regulatory elements that control OR promoters are not olfactory specific. Still, our inability to elicit even leaky CRE recombination in mESCs suggests that a specific transcriptional machinery within the OSN lineage is needed to drive OR promoter activation.