A Group of Olfactory Receptor Alleles that Encode Full Length Proteins are Down-Regulated as Olfactory Sensory
Richard C Krolewski1,2, Brian Lin1, Samuel Stampfer3,2
1Program in Cell Molecular and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, United States.
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.
Insights
Researchers identified 43 olfactory receptors (ORs) with unusual expression patterns. These atypical ORs may be non-functional, despite lacking obvious sequence abnormalities, offering new insights into smell receptor regulation.
Area of Science:
- Neuroscience
- Genetics
- Olfactory receptor research
Background:
- Olfactory receptors (ORs) are crucial for the sense of smell.
- ORs include functional genes and pseudogenes, identified by mutations.
- Nonfunctional ORs are initially expressed during neuronal differentiation but are later downregulated or their expressing neurons die.
Purpose of the Study:
- To investigate the expression patterns of olfactory receptors during neuronal differentiation.
- To identify olfactory receptors with atypical expression profiles.
- To explore potential non-functionality of these atypical olfactory receptors.
Main Methods:
- Transcriptomic analysis of FACS-isolated cells from transgenic mice at distinct olfactory sensory neuron (OSN) developmental stages.
- Analysis of 1094 unique olfactory receptors across OSN progression.
- Protein and promoter sequence analysis of atypical ORs.
Main Results:
- The vast majority of olfactory receptors (ORs) exhibited typical expression patterns, peaking in mature OSNs.
- 43 ORs, including known pseudogenes, showed atypical expression, with declining mRNA levels in mature OSNs.
- Sequence analysis revealed no obvious abnormalities in the atypical OR group compared to typical ORs.
Conclusions:
- Atypical olfactory receptor (OR) expression patterns suggest potential non-functionality.
- The study identified specific ORs that deviate from expected expression profiles.
- Further investigation is needed to understand the functional implications of these atypical ORs despite normal sequence analysis.
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