Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice.
Cyclic nucleotide-gated ion channels in olfactory sensory neurons (OSNs) are hypothesized to play a critical role in olfaction. However, it has not been demonstrated that the cAMP signaling is required for olfactory-based behavioral responses, and the contributions of specific adenylyl cyclases to olfaction have not been defined. Here, we report the presence of adenylyl cyclases 2, 3, and 4 in olfactory cilia. To evaluate the role of AC3 in olfactory responses, we disrupted the gene for AC3 in mice. Interestingly, electroolfactogram (EOG) responses stimulated by either cAMP- or inositol 1,4,5-triphosphate- (IP3-) inducing odorants were completely ablated in AC3 mutants, despite the presence of AC2 and AC4 in olfactory cilia. Furthermore, AC3 mutants failed several olfaction-based behavioral tests, indicating that AC3 and cAMP signaling are critical for olfactory-dependent behavior.
Wong
S T
ST
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Trinh
K
K
Hacker
B
B
Chan
G C
GC
Lowe
G
G
Gaggar
A
A
Xia
Z
Z
Gold
G H
GH
Storm
D R
DR
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D002923:Cilia / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D018390:Gene Targeting; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D000857:Olfaction Disorders / Q000201:enzymology* / Q000235:genetics*; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013268:Stimulation, Chemical
D007527:Isoenzymes; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C100622:adenylyl cyclase 2; C406262:adenylyl cyclase 4