Gene Expression Profiles Of Main Olfactory Epithelium In Adenylate Cyclase 3 Knockout Mice

Adenylate Cyclase 3(AC3) plays an important role in the olfactory sensation signaling pathway in mice. AC3 deficiency leads to disorders of olfactory detection. However, it is still unknown whether AC3 deficiency affects gene expression or signal transduction pathways related to it within the main olfactory epithelium(MOE). In this study, gene microarrays were used to screen differentially expressed genes in MOE from the AC3 knockout(AC3-/-) and the wild-type(AC3+/+) mice. The differentially expressed genes identified were subjected tobioinformatic analysis and verified by q RT-PCR. Results showed that gene expression in MOE from AC3-/- mice was significantly altered, compared with AC3+/+ mice. Of the 41266 gene probes, there are 3379 had greater than 2-fold differential expression between AC3-/- and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up-regulated, and 1988 were down-regulated, including 407 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are epigenetic regulated. Gene Ontology(GO) analysis showed that these differentially expressed genes were involved in substrate binding, cell cycle, cell growth and development. Pathway analysis revealed that AC3 deletion had a significant impact on olfactory signaling, cell growth and apoptosis related signaling pathways, and several gated ion channel signaling pathways. The differentially expressed olfactory receptor genes were predominantly located on mouse chromosomes 2, 7, 9, 10 and 19. The differentially expressed epigenetic related genes were predominantly located on mouse chromosomes 2, 6, 7 and 9. Quantitative RT-PCR verification of the differentially expressed epigenetic related genes, olfactory receptors, ion transporter related genes, nerve cell development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75 NTR, Hinfp, Gadd45 b, Tet3 etc. were significantly up-regulated(p<0.01), while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6 b, H2 BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated(p<0.01), which was consistent with results of the microarray screening. In all, AC3 may influence with the olfactory signal transduction and function through the regulation of differentially expressed genes in mouse MOE.