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

被引:339
作者
Wong, ST
Trinh, K
Hacker, B
Chan, GCK
Lowe, G
Gaggar, A
Xia, ZG
Gold, GH
Storm, DR [1 ]
机构
[1] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
[2] Univ Washington, Dept Environm Hlth & Toxicol, Seattle, WA 98195 USA
[3] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA
关键词
D O I
10.1016/S0896-6273(00)00060-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:487 / 497
页数:11
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