人肾素转基因小鼠的建立

Studies on Transgenic Mice Harboring The Human Renin Gene

为研究人肾素基因在体内的功能和建立其药物干预实验的动物模型 ,采用显微注射法 ,将纯化的人肾素基因导入小鼠受精卵 ,再培育成转基因小鼠 .通过DIGDNA印迹和PCR分析 ,进行转基因整合检测 .在出生的 13只子代鼠中 ,得到一只转基因阳性鼠 .整合率为 7 7% ,有效率 0 3% ,转基因已稳定传代 .RT PCR显示转基因阳性鼠的肾、心和肺组织中有肾素基因表达 ,而在肝脏与骨骼肌中则未检测到 .阳性鼠血浆肾素活性较对照鼠明显升高 ,而肾与心脏组织的肾素活性则无明显变化 .

In order to determine the function of, in vivo, human rennin gene and to establish an animal model for drug inhibitory experiment of human rennin, the transgenic mice were produced via microinjection method by which the mice fertilized ova were injected with the purified human rennin gene. Assay of transgene integration was determined by DIG DNA blotting hybridization and PCR analysis. One Mouse among 13 survived mice was the positive transgenic mouse. Integration efficiency was 7.7%. Overall efficiency was 0.3%. Transgene was steadily transfered from generation to generation. The human rennin transgene was found, by RT-PCR, to be expressed in the heart, kidney, and lung of transgenic mice, but not in the liver or skeletal muscle. The mean levels of rennin activity in the plasma of the transgenic mice was also found to be significantly higher than that of the control mice. However, no significant differences were seen in the mean levels of rennin activities in the kidney and heart between transgenic and control mice. These transgenic mice will provide the opportunity to investigate the rennin gene function in circulation (or tissue) rennin angiotensin system, and may, provide an experimental model for testing human rennin inhibitors as drugs.