Structure and function of renin and prorenin.

1)肾的X线结构用X线分析在2.5A^^ 3.0A^^分辨率下测定了小鼠颌下肾素和重组人肾素的三维结构。2)加工酶克隆小鼠颌下腺prorenin加工酶cDNA并测定其完整核苷酸序列，证实prorenin加工酶与proEGF加工酶相同。加工酶将下颌骨前肾素加工成肾素，而不是肾前肾素，提示其器官特异性。目前已经确定了几种肾前肾素加工酶或激素原酶和前酶的候选酶（酵母Kex2样加工酶），并确定了它们的完整氨基酸序列。这些结果表明，不仅是促泌素，激素原和酶原也以底物特异性或器官特异性的方式加工。3)肾素和血管紧张素原在体内的基因调控通过杂交将人肾素和血管紧张素原基因分别或同时引入小鼠体内。携带这两种人类基因的菌株表现出长期持续的血压升高。因此，我们建立了新的转基因小鼠（筑波高血压小鼠）作为人类高肾素高血压的第一个模型。

1) X ray structure of reninThree-dimensional structure of mouse submaxillary renin and recombinant human renin have been determined at 2.5A^^ﾟ - 3.0A^^ﾟ resolution by X-ray analysis.2) Processing enzymesThe cDNA of prorenin processing enzyme in mouse submaxillary glands was cloned and its complete nucleotide sequence was determined, identify that prorenin processing enzyme is identical with proEGF processing enzyme. The processing enzyme processed the submaxillary prorenin to renin, but not kidney prorenin suggesting its organ specificity.Several candidates (yeast Kex2 like processing enzyme) for kidney prorenin processing enzyme or for prohormones and proenzymes have been identified and their complete amino acid sequences have been determined. These results suggests that not only prorenin but also prohormones and proenzymes are processed by substrate- or organ-specific manner.3) Gene regulation of renin and angiotensinogen in vivoHuman renin and human angiotensinogen genes both separately and in concert have been introduced into mice by cross-mating.Strains carring both the human genes demonstrated a chronically sustained increase in blood pressure. Thus, we have established new transgenic mice (Tsukuba Hypertensive Mice) as the first model of human high renin hypertension.