| The human nose is considered a luxury, but in the rest of the animal world, detecting chemicals in the environment is critical to the survival success of the organism. This reflexes in the large percentage of the genome that had been set a side for odorant receptor gene families. In the mouse genome, it is estimated that there are approximately 1000 genes. In addition, there are genes encoding down stream signaling pathway(s) that are involved in transducing chemical signals into electrical responses in olfactory sensory neurons (OSNs) (for review see (Mombaerts 1999; Firestein 2001)).; Biochemical studies on cilia preparations demonstrated that odorants could induce an increase in either IP3 or CAMP production (Boekhoff et al., 1990; Breer and Boekhoff, 1991; Huque and Bruch, 1986). Thus, it has been hypothesized that distinct signal transduction pathways may be involved in activation of OSNs by subsets of odorant receptors (reviewed in Restrepo et al., 1996). However, recent gene disruption studies with Golf and CNG mutant mice (Belluscio et al., 1998; Brunet et al., 1996) suggest that a cyclic nucleotide signal transduction pathway may play a central role in odorant detection. Thus, it is essential to determine if the cyclic nucleotide signal is either cAMP or cGMP. If CAMP increases are required for olfactory signaling, which adenylyl cyclase(s) is critical in the generation of olfactory signal?; The type II adenylyl cyclase (AC2), type IV adenylyl cyclase (AC4) and type III adenylyl cyclase (AC3) are all found in the olfactory epithelium (Wong, Trinh et al. 2000). However, only AC3 is abundantly expressed and the protein is localized in the cilia layer (Pfeuffer, Mollner et al. 1989). Based on this expression pattern, it is likely that AC3 may play a role in odorant induce cAMP increases in OSNs.; This study utilized gene targeting to examine the role of the AC3 in olfactory signal transduction. Homozygous AC3 mice show an ablation in the electrophysiological response of primary olfactory sensory neurons to a wide variety of odorants. A large percentage of the AC3 homozygotes are unable to survive. However, the rare surviving homozygotes show behavioral responses to a small number of compounds. Some of these compounds are putative pheromones and these compounds induce electrophysiological responses in the vomeronasal epithelium. |
