Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice.

Zhenshan Wang,Jing Zhang,Zhe Zhang,Yongchao Li,Yingtao Luo,Yunpeng Zhai,Daniel Storm,Yanfen Zhou,Dong Yang,Runlin Ma

doi:10.3390/ijms161226107

Abstract

Adenylyl Cyclase 3 (AC3) plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE). In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/−) and wild-type (AC3+/+) mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels 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 425 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 involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE.

Highlights

Olfaction is important in the lives of both animals and humans
To define the effects of Adenylyl Cyclase 3 (AC3) gene knockout on gene expression in the mouse main olfactory epithelium (MOE), the Agilent Mouse Genome 4 X 44K chip was used for hybridization
After comparison of all genes expressed in the MOE of AC3 ́{ ́ and AC3+/+ mice, we found that among the 41266 gene probes, 3379 had greater than a 2.0-fold change in expression levels between AC3 ́{ ́ and AC3+/+ mice

Summary

Introduction

The main olfactory epithelium (MOE) is the primary olfactory organ in mammals for the perception of odor molecules [1]. Within the MOE, are layers of cells with the mature olfactory neurons on the top and the immature olfactory neurons on the bottom. The mature olfactory neurons have sensory cilia which express the primary signaling components for olfaction including odorant receptors [2], Golf [3], AC3 [4] and the cyclic nucleotide gated ion channel (CNG channel) [5]. The main role of AC3 is to catalyze the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) which activates the CNG for exchange of calcium ions and chloride ion efflux, transmembrane protein (TMEM) channels, to cause membrane depolarization [6,7,8,9]. AC3 deficient mice exhibit olfactory dysfunction, adult obesity and malfunction of smell related behaviors [4,10,11,12,13]

Results

Discussion

Conclusion