Su Ting, Zhang Qing-Yu, Zhang Jianhua, Swiatek Pam, Ding Xinxin
Wadsworth Center, New York State Department of Health and School of Public Health, State University of New York at Albany, Albany, New York 12201-0509, USA.
Drug Metab Dispos. 2002 May;30(5):548-52. doi: 10.1124/dmd.30.5.548.
Rat CYP2A3 and mouse CYP2A5 are predominantly expressed in the olfactory mucosa. CYP2A3 is also expressed in the lung at a low level, whereas CYP2A5 is expressed in several additional tissues. To better understand the transcriptional regulation of the CYP2A genes, transgenic mice were generated with a full-length CYP2A3 gene fragment containing 3.4 kilobases of the 5'-flanking region. CYP2A3 mRNA was detected in the brain and olfactory bulb in four transgenic mouse lines, in the olfactory mucosa in three lines, and in kidney, liver, lung, and small intestine in two lines. Thus, the expression of the CYP2A3 transgene mimicked the tissue distribution pattern of mouse CYP2A5 rather than that of rat CYP2A3. Furthermore, the levels of CYP2A3 mRNA were very low in all lines examined, suggesting that more distal regulatory regions may be involved in the abundant expression of the CYP2A genes in the olfactory mucosa.
大鼠CYP2A3和小鼠CYP2A5主要在嗅觉黏膜中表达。CYP2A3在肺中也有低水平表达，而CYP2A5在其他几个组织中表达。为了更好地理解CYP2A基因的转录调控，构建了转基因小鼠，其携带一个包含3.4千碱基5'侧翼区域的全长CYP2A3基因片段。在四个转基因小鼠品系的大脑和嗅球中检测到了CYP2A3 mRNA，在三个品系的嗅觉黏膜中检测到，在两个品系的肾脏、肝脏、肺和小肠中检测到。因此，CYP2A3转基因的表达模拟了小鼠CYP2A5的组织分布模式，而非大鼠CYP2A3的模式。此外，在所检测的所有品系中，CYP2A3 mRNA水平都非常低，这表明更远端的调控区域可能参与了CYP2A基因在嗅觉黏膜中的大量表达。
