Abstract
The mammalian main olfactory pathway detects myriad volatile chemicals using >1,000 odorant receptor (OR) genes, which are organized into two phylogenetically distinct classes (class I and class II). An important question is how these evolutionarily conserved classes contribute to odor perception. Here, we report functional inactivation of a large number of class I ORs in mice via identification and deletion of a local cis-acting enhancer in the class I gene cluster. This manipulation reduced expression of half of the 131 intact class I genes. The resulting class I-depleted mice exhibited a significant reduction in the number of glomeruli responding to carboxylic acids—chemicals associated with microbial action and body odors. These mice also exhibit a change in odor perception marked by a selective loss of behavioral aversion to these compounds. Together, our data demonstrate that class I ORs play a critical role in representing a class of biologically relevant chemosignals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2687-2697.e4 |
| Journal | Current Biology |
| Volume | 29 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 19 2019 |
Funding
This work was supported by grants from NIH / NIDCD , R01DC013576 (T.B.) and R03DC014565 (A.D.), and the Deutsche Forschungsgemeinschaft CI 222/1-1 (A.C.). We thank Bill Kath for help with bioinformatics, Amanda Menzie and Maddie Ratkowski for technical support, Rodrigo Pacifico for generation of early transgenic constructs, Lynn Doglio and the Transgenic and Targeted Mutagenesis Facility at Northwestern University for transgenic mouse production, Pieter Faber and The Genomics Facility at University of Chicago for high-throughput sequencing, and Paul Feinstein for input and comments on the manuscript. This work was supported by grants from NIH/NIDCD, R01DC013576 (T.B.) and R03DC014565 (A.D.), and the Deutsche Forschungsgemeinschaft CI 222/1-1 (A.C.). We thank Bill Kath for help with bioinformatics, Amanda Menzie and Maddie Ratkowski for technical support, Rodrigo Pacifico for generation of early transgenic constructs, Lynn Doglio and the Transgenic and Targeted Mutagenesis Facility at Northwestern University for transgenic mouse production, Pieter Faber and The Genomics Facility at University of Chicago for high-throughput sequencing, and Paul Feinstein for input and comments on the manuscript. A.C. and T.B. conceived of the project. A.C. A.D. and T.B. designed the experiments. A.C. generated mouse strains and performed behavioral experiments, imaging, RNA isolation, and histological analyses; A.D. performed behavioral experiments; S.K. performed RNA isolation and qPCR analysis; and A.S. performed RNA isolation, in situ hybridization, and RNA-seq bioinformatics analyses. A.C. and T.B. wrote the manuscript with input from all authors. The authors declare no competing interests.
Keywords
- carboxylic acids
- enhancer
- monoallelic expression
- mouse
- odor aversion
- odorant receptor
- olfaction
- olfactory bulb
- olfactory epithelium
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Agricultural and Biological Sciences