Genetic Depletion of Class I Odorant Receptors Impacts Perception of Carboxylic Acids

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. •Deletion of an enhancer reduces expression of class I odorant receptors in mice•Class I receptor depletion selectively reduces acid responses in the olfactory bulb•Loss of class I receptors and glomeruli reduces behavioral aversion to acids•Class I odorant receptors are critical for the perception of carboxylic acids Cichy et al. show that deleting a cis-acting enhancer in the class I odorant receptor cluster reduces class I receptor gene choice. The resulting class I-depleted mice exhibit reduced functional and behavioral responses to carboxylic acids. The results demonstrate a role for class I odorant receptors in detecting an important class of odorants.