多巴胺D5受体转基因小鼠的建立

目的建立人多巴胺D5受体突变基因F173 L（D5F173L）,S390G（D5S390G）及正常人D5基因（hD5 WT）的转基因小鼠,利用该转基因动物模型来研究D5受体在原发性高血压中的发病机制。方法利用显微注射的技术将插入CMV启动子下游的D5F173L,D5S390G及hD5 WT基因的转基因载体注射入C57BL/6小鼠体内,建立多巴胺D5F173L,D5S390G及hD5 WT的转基因小鼠。通过PCR鉴定转基因小鼠的基因型。利用Western Blotting方法鉴定该受体蛋白在肾脏的表达情况。使用智能无创血压测量仪测量转基因小鼠的血压值。结果分别建立了多巴胺D5F173L,D5S390G及hD5 WT转基因C57BL/6小鼠,Western Blotting方法鉴定结果显示,与非转基因C57BL/6小鼠比较,D5转基因小鼠D5受体在肾脏有较高的表达。3-6月龄D5 F173L转基因小鼠的收缩压、舒张压和平均动脉血压均明显高于多巴胺D5S390G及hD5 WT转基因小鼠（n=6-8,P〈0.05）。结论多巴胺D5受体在原发性高血压发病中具有重要作用,但作用机理还有待于进一步研究。

The Establishment of Human Dopamine D5 Receptor Transgenic Mice

Objective To establish mutanted wild type human dopamine DSR gene transgenic mice and investigate the role of dopamine DSR in the development of hypertension. Methods Transgenic mice were created by microinjection of the constructs for pcDNA-D5F173L,pcDNA-DSS390G and pcDNA-DSWT. The genotype of transgenic founders and its offsprings were detected by PCR. The expression of dopamine D5 receptor was analyzed by Western Blotting. The non-invasive method was used to analyze the blood pressure of transgenic mice and negative littermate controls. Results The transgenic mice with high expression levels of D5F173L, D5S390G, and wild type D5 genes were established. The systolic, diastolic and mean arterial blood pressures of D5F173L transgenic mice were higher than DSS390G and wild type D5 gene transgenic mice. Conclusion The results suggest that the dopamine D5 receptor may play an important role in the development of essential hypertension. However, the mechanism remains to be not clear.