GENERAL ANOSMIA CAUSED BY A TARGETED DISRUPTION OF THE MOUSE OLFACTORY CYCLIC NUCLEOTIDE-GATED CATION CHANNEL

Olfactory neurons transduce the binding of odorants into membrane depo larization. Two intracellular messengers, cyclic AMP (cAMP) and inosit ol trisphosphate (IP3), are thought to mediate this process, with cAMP generating responses to some odorants and IP3 mediating responses to others. cAMP causes membrane depolarization by activating a cation-sel ective cyclic nucleotide-gated (CNG) channel. We created a mutant ''kn ockout'' mouse lacking functional olfactory CNG channels to assess the roles of different second messenger pathways in olfactory transductio n. Using an electrophysiological assay, we find that excitatory respon ses to both cAMP- and IP3-producing odorants are undetectable in knock out mice. Our results provide direct evidence that the CNG channel sub serves excitatory olfactory signal transduction, and further suggest t hat cAMP is the sole second messenger mediating this process.