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Gene Review

Adcy3  -  adenylate cyclase 3

Mus musculus

Synonyms: AC-III, AC3, ATP pyrophosphate-lyase 3, Adenylate cyclase type 3, Adenylate cyclase type III, ...
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Psychiatry related information on Adcy3

  • The complete loss of MOE-mediated olfaction in type-3 adenylyl cyclase knockout mice (AC3-/-) allowed us to examine chemosensory functions of the VNO in the absence of signaling through the MOE [1].

High impact information on Adcy3

  • To evaluate the role of AC3 in olfactory responses, we disrupted the gene for AC3 in mice [2].
  • One-week-old male and female mice of the A, BALB/c (C), and C3H/He (C3) strains and of the AC3 and CC3 F1 hybrids were treated with a single dose (300 mg/kg s.c.) of urethan and then kept without further treatment until 30 and 40 weeks (males) or 30 and 65 weeks (females) [3].
  • Immunoblot analysis revealed that AC5/6 and AC3 are expressed in parotid glands [4].
  • Maximum stimulation of enzyme activity was increased in each of the AC transfectants to varying extents. alpha2A/D-AR activation elicited enzyme type-specific responses. alpha2-AR activation inhibited the effect of isoproterenol in control transfectants, and this action was magnified in AC III transfectants [5].
  • When used in in vitro fertilization, spermatozoa from these AC3(-/-) mice produced few embryos, but their fertilizing ability was restored after removal of the zona pellucida [6].

Biological context of Adcy3

  • Inactivation of the AC3 gene did not have overt effects on spermatogenesis; however, AC3(-/-) males were subfertile with only three litters generated by 11 males over a period of 6 months [6].
  • Serologic similarity between factor 4 and the binding site of MAb AC3 was also determined [7].
  • We conclude that signaling through AC3 in the MOE is obligatory for male sexual behavior, male-male aggressiveness, and the detection of some pheromones [8].

Anatomical context of Adcy3

  • Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility and spermatozoon function [6].
  • These data support the hypothesis that AC3 is required for normal spermatid or spermatozoa function and male fertility [6].
  • As previously reported in rat, AC3 mRNA is expressed in mouse testes and localized, together with soluble AC mRNA, mainly in postmeiotic germ cells [6].
  • Molecular phenotyping demonstrated that the receptor expressing cells in the cribriform mesenchyme co-express key elements, including Galpha(olf), ACIII and OMP, characteristic for olfactory neurons in the nasal epithelium [9].
  • Furthermore, adenylyl cyclase activity in membranes prepared from the MOE of wild-type mice, but not AC3-/- mice, is stimulated by 2-heptanone, a mouse pheromone [8].

Associations of Adcy3 with chemical compounds

  • 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 [2].
  • Immunoblots were analyzed for the presence of transduction components enriched in olfactory cilia: adenylyl cyclase type III (ACIII), heterotrimeric G-protein subunit Galphaolf and the 1 C2 isoform of phosphodiesterase (PDE 1 C2) [10].
  • Lung and colon tumors were induced in A/J, C3H, and A/J X C3H (AC3) mice by administering 16 mg/kg vinyl carbamate followed by 6 weekly doses of 12 mg/kg azoxymethane (AOM) [11].
  • Dexamethasone and piroxicam reduced the multiplicity of colon and lung tumors in A/J and AC3 mice, demonstrating the advantage of a combined colon and lung bioassay [11].
  • The AC3 mutant had expanded deoxyribonucleoside triphosphate pools [12].

Other interactions of Adcy3

  • Of particular interest were AC3 and AC8, located in the same regions as, and hence possibly directly associated with, specific cell surface receptors and G proteins that are able to regulate the spermatozoon's acquisition and maintenance of fertilizing ability via changes in AC/cAMP [13].

Analytical, diagnostic and therapeutic context of Adcy3

  • Two MAbs, CB6 (C. tropicalis and C. albicans A specific) and AC3 (C. tropicalis and C. albicans A and B specific), functioned in place of polyclonal antisera in the serotyping of C. albicans by immunofluorescence [7].


  1. Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Trinh, K., Storm, D.R. Nat. Neurosci. (2003) [Pubmed]
  2. Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Wong, S.T., Trinh, K., Hacker, B., Chan, G.C., Lowe, G., Gaggar, A., Xia, Z., Gold, G.H., Storm, D.R. Neuron (2000) [Pubmed]
  3. Quantitative analysis of genetic susceptibility to liver and lung carcinogenesis in mice. Dragani, T.A., Manenti, G., Della Porta, G. Cancer Res. (1991) [Pubmed]
  4. The type 8 adenylyl cyclase is critical for Ca2+ stimulation of cAMP accumulation in mouse parotid acini. Watson, E.L., Jacobson, K.L., Singh, J.C., Idzerda, R., Ott, S.M., DiJulio, D.H., Wong, S.T., Storm, D.R. J. Biol. Chem. (2000) [Pubmed]
  5. Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. Integration of stimulatory and inhibitory input to the effector adenylyl cyclase. Marjamaki, A., Sato, M., Bouet-Alard, R., Yang, Q., Limon-Boulez, I., Legrand, C., Lanier, S.M. J. Biol. Chem. (1997) [Pubmed]
  6. Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility and spermatozoon function. Livera, G., Xie, F., Garcia, M.A., Jaiswal, B., Chen, J., Law, E., Storm, D.R., Conti, M. Mol. Endocrinol. (2005) [Pubmed]
  7. Monoclonal antibodies against Candida tropicalis mannan: antigen detection by enzyme immunoassay and immunofluorescence. Reiss, E., de Repentigny, L., Kuykendall, R.J., Carter, A.W., Galindo, R., Auger, P., Bragg, S.L., Kaufman, L. J. Clin. Microbiol. (1986) [Pubmed]
  8. Pheromone detection in male mice depends on signaling through the type 3 adenylyl cyclase in the main olfactory epithelium. Wang, Z., Balet Sindreu, C., Li, V., Nudelman, A., Chan, G.C., Storm, D.R. J. Neurosci. (2006) [Pubmed]
  9. Expression of olfactory receptors in the cribriform mesenchyme during prenatal development. Schwarzenbacher, K., Fleischer, J., Breer, H., Conzelmann, S. Gene Expr. Patterns (2004) [Pubmed]
  10. Comparison of mechanical agitation and calcium shock methods for preparation of a membrane fraction enriched in olfactory cilia. Washburn, K.B., Turner, T.J., Talamo, B.R. Chem. Senses (2002) [Pubmed]
  11. Chemoprevention: mouse colon and lung tumor bioassay and modulation of DNA methylation as a biomarker. Pereira, M.A., Tao, L.H., Wang, W., Gunning, W.T., Lubet, R. Exp. Lung Res. (2005) [Pubmed]
  12. High level of aphidicolin resistance with multiple mutations in mouse FM3A cell mutants. Ito, M., Matsuhashi, M., Seno, T., Ayusawa, D. Somat. Cell Mol. Genet. (1990) [Pubmed]
  13. Evidence for multiple distinctly localized adenylyl cyclase isoforms in mammalian spermatozoa. Baxendale, R.W., Fraser, L.R. Mol. Reprod. Dev. (2003) [Pubmed]
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