Grant-in-Aid for Specially Promoted Research.
|Research Institution||University of Tsukuba|
MURAKAMI Kazuo Univ. of Tsukuba, Inst. of Appl. Biochem., Prof., 応用生物化学系, 教授 (70110517)
坂部 知平 高エネルギー物理学研究所放射光施設, 教授 (30022601)
FUKAMIZU Akiyoshi Univ. of Tsukuba, Inst. of Appl. Biochem., Instructor, 応用生物化学系, 講師 (60199172)
NAKAYAMA Kazuhisa Univ. of Tsukuba, Inst. of Biol.Sci., Instructor, 生物科学系, 講師 (40192679)
宮崎 均 筑波大学, 応用生物化学系, 講師 (40183636)
|Project Fiscal Year
1989 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥208,000,000 (Direct Cost : ¥208,000,000)
Fiscal Year 1992 : ¥30,000,000 (Direct Cost : ¥30,000,000)
Fiscal Year 1991 : ¥35,000,000 (Direct Cost : ¥35,000,000)
Fiscal Year 1990 : ¥65,000,000 (Direct Cost : ¥65,000,000)
Fiscal Year 1989 : ¥78,000,000 (Direct Cost : ¥78,000,000)
|Keywords||Renin / Prorenin / Angiotensinogen / X ray analysis / Embryonic Engineering / Processing / Transgenic mice / Hypertension / レニン / プロレニン / アンジオテンシノーゲン / X線結晶解析 / 発生工学 / プロセッシング / トランスジェニック・マウス / 高血圧 / 高血圧マウス / 遺伝子工学 / プロテイン・エンジニアリング / 組織特異的発現|
1) X ray structure of renin
Three-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 enzymes
The 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 vivo
Human 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.