Evaluation of CMV and KAP promoters for driving the expression of human CYP4F2 in transgenic mice.
Evaluation of CMV and KAP promoters for driving the expression of human CYP4F2 in transgenic mice.
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DOI：
10.3892/ijmm.2011.787
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发表时间：
2011-12
影响因子：
5.4
通讯作者：
Guangrui Lai;Xiaoliang Liu;Jingjing Wu;Hong Liu;Yanyan Zhao
中科院分区：
文献类型：
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作者：
Guangrui Lai;Xiaoliang Liu;Jingjing Wu;Hong Liu;Yanyan Zhao
与我们先前建立的肾脏雄激素调节蛋白（KAP）启动子CYP 4F 2转基因小鼠模型（主要表现为肾脏CYP 4F 2过表达）相比，细胞色素P450 4F 2（CYP 4F 2）在多器官中表达的转基因小鼠模型有望阐明20-羟基二十碳四烯酸（20-HETE）在血压调节中的作用。建立了一种由细胞巨病毒（CMV）启动子驱动的新型CYP 4F 2转基因小鼠模型，并通过PCR和随后的测序进行了鉴定。对CMV-CYP 4F 2转基因小鼠的广泛研究表明，CYP 4F 2仅在肝脏中表达，而尿液、肾脏和血液中的20-HETE水平不受影响，收缩压也未发生变化。这与KAP-CYP 4F 2转基因小鼠相反，后者通过肾脏过度表达CYP 4F 2发挥20-HETE的降压作用。此外，CYP 4F 2在KAP-CYP 4F 2中压倒了内源性肾脏Cyp 4a家族mRNA水平，但在CMV-CYP 4F 2转基因小鼠中没有。这些结果支持了肾CYP 4F 2过表达导致尿液和血液中20-HETE升高可能是血压升高的原因的观点。CMV启动子没有指导CYP 4F 2表达到广泛的组织和器官中，试图阐明20-HETE的作用。
A transgenic mouse model in which cytochrome P450 4F2 (CYP4F2) was expressed in multiple organs was expected to clarify the role of 20-hydroxyeicosatetraenoic acid (20-HETE) in the regulation of blood pressure, compared with our previously established kidney androgen-regulated protein (KAP) promoter CYP4F2 transgenic mouse model which predominantly showed renal overexpression of CYP4F2. A novel CYP4F2 transgenic mouse model driven by the cyto-megalovirus (CMV) promoter was generated and identified by PCR and subsequent sequencing. Extensive study of CMV-CYP4F2 transgenic mice demonstrated that CYP4F2 was exclusively expressed in the liver, while 20-HETE levels in the urine, kidney and blood were not affected, and there was no resulting change in the systolic blood pressure. This was in contrast to KAP-CYP4F2 transgenic mice which exerted prohypertensive action of 20-HETE resulting from the renal overexpression of CYP4F2. In addition, CYP4F2 overwhelmed the endogenous renal Cyp4a family mRNA levels in the KAP-CYP4F2 but not in the CMV-CYP4F2 transgenic mice. These results support the idea that overexpression of renal CYP4F2, leading to high 20-HETE in the urine and blood, may account for the elevated blood pressure. The CMV promoter did not direct CYP4F2 expression into extensive tissues and organs in an attempt to clarify the action of 20-HETE.