Transgenic Mice Carrying Human Renin Gene And Angiotensinogen Gene Initially Established

Initial study on the production of transgenic mice harboring human renin and human angiotensinogen genes.Primary hypertension is a complex, multifactorial and polygenic disease and little progress has been made in unraveling its etiology. It has been fully elucidated that there exists the relationship between human RAS function and the onset and development of hypertension based not only on genetic linkage analysis of RAS conponent genes but also on numerous clinical observations. This desserta-tion research was designed to investigate relatioship between human renin and human angiotensinogen genes and hypertension using transgenic animal procedure. Plasmid DNAs were prepared by alkali lysis and purified with polyethylene glycol 8000. Restriction enzyme analysis show that both genes are well-constructed suitable for transgenic animal experiment. By means of pronucleus mi-croinjection, two genes were tranfered into the mouse fertilized eggs. Thirty-four pseudopregnant recipient mice were operated oviduct transfer. Eleven of them were pregnant and 40 pups were born. Tail DNA of pups were isolated and hybridized with the probes from human renin and human angiotensinogen genes. Four offsprings were proved harboring human renin gene. Integration rate of foreign gene is 10%. Southern blot show negatire result of human angiotensi-noen gene. Total RNAs from pup mouse kidneys positively-hybridized to human renin gene probe were isolated and transfered onto nylon membrane and then hybridized to human renin cDNA probe. High levels of transgene mRNAs were detective in two transgenic mouse kidneys. The findings above demonstrat that injected human renin gene can be integreted into mouse genomic DNA and expressed highly in transgenic mouse kidneys. This work has laid a solid foundation for the further study on constructing of hypertensive transgenic mice harboring human renin and human angiotensinogen genes.