Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice

Neuron. 2000 Sep;27(3):487-97. doi: 10.1016/s0896-6273(00)00060-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Avoidance Learning
  • Behavior, Animal
  • Cilia / metabolism
  • Cyclic AMP / metabolism
  • Electrophysiology
  • Gene Targeting*
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Isoenzymes / genetics
  • Mice
  • Mice, Transgenic / genetics
  • Olfaction Disorders / enzymology*
  • Olfaction Disorders / genetics*
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / metabolism
  • Signal Transduction
  • Stimulation, Chemical


  • Isoenzymes
  • Inositol 1,4,5-Trisphosphate
  • Cyclic AMP
  • Adenylyl Cyclases
  • adenylyl cyclase 2
  • adenylyl cyclase 4