It is believed that odor transduction in the mammalian main olfactory system only involves the cAMP-signaling pathway. Here, we report on odor responsiveness in mice with a disrupted cyclic nucleotide-gated (CNG) channel subunit A2. Several odorants, including putative pheromones, can be detected and discriminated by these mice behaviorally. These odors elicit responses in the olfactory epithelium, main olfactory bulb, and olfactory (piriform) cortex of CNGA2 knock-out mice. In addition, responses to odors detected by CNGA2 knock-out mice are relatively insensitive to inhibitors of the cAMP pathway. These results provide strong evidence that cAMP-independent pathways in the main olfactory system of mammals participate in detecting a subset of odors.
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