A Group of Olfactory Receptor Alleles that Encode Full Length Proteins are Down-Regulated as Olfactory Sensory Neurons Mature.

ABSTRACT

The family of olfactory receptors (ORs) subserves the sense of smell and includes both functional alleles and pseudogenes, the latter identified by mutations resulting in frame shift or premature truncation. During neuronal differentiation, nonfunctional ORs are expressed initially but then are switched out, and/or the olfactory sensory neurons (OSNs) expressing them die. We carried out a transcriptomic analysis of FACS-isolated cells from ΔSox2-eGFP, Neurog1-eGFP BAC and ΔOMP-eGFP strains of uninjured and olfactory bulbectomized transgenic mice that correspond to distinct stages in the progression from globose basal cell stem cells to fully mature OSNs. We analyzed the expression pattern of 1094 unique receptors across this progression and found that the vast majority were characterized by a typical and expected pattern of expression; i.e., levels of OR mRNA peaking in mature OSNs. However, 43 ORs, including several known pseudogenes, were different, such that mRNA expression declined in the mature OSNs relative to earlier stages. Protein and promoter sequence analysis of the atypical group did not uncover any obvious differences between them and more typical ORs. Nonetheless, the pattern of expression suggests that atypical ORs may be non-functional despite the lack of any obvious abnormality in the sequence analyses.