TSUKUBA HYPERTENSIVE MICE TRANSGENIC MICE CARRYING BOTH HUMAN RENIN AND HUMAN ANGIOTENSINOGEN GENES

Molecular and in vivo studies of renin-angiotensin system (RAS) have been developed by introducing new techniques.1) First, human renin was isolated and characterized after about half million-fold purification by introducing the new affinity column, pepstatin column. Secondly, molecular biology including recombinant DNA technology has made great progress on studies of renin and angiotensinogen as well as their genes. The cDNA of human renin precursor was isolated and the primary structure of human renin precursor was deduced from its nucleotide sequences. Genomic DNAs of human renin precursor and human angiotensinogen were also isolated and the structures of their exons and introns in addition to 5'- and 3'-flanking regions were determined. Thirdly, transgenic mice carrying both human renin and human angiotensinogen genes were produced as the first animal model for human hypertension which had simple and clear human genetic background. The hypertensive transgenic mice were named as ''Tsukuba Hypertensive Mice''.