Abstract
Transgenic animals are used to study the function, regulation and in vivo expression of genes. The effects of the genes of the renin-angiotension system on blood pressure regulation and hypertension were investigated in transgenic rats. The role of the renin-angiotensin system in the development of cardiovascular hypertrophy of hypertensive renal damage was analysed, as well as its interaction with other hormonal systems, i.e. adrenal steroids. The development of a transgenic rat strain carrying the mouse REN-2 gene has provided a new model of hypertension with systolic blood pressure values of 200 mmHg. This model is characterised by low active plasma renin, hyperproreninaemia and high expression of renin in the adrenal gland and other extrarenal tissues. Transgenic rats with thehuman components of the renin-angiotensin system expressed the human renin and angiotensinogen proteins which interacted species-specifically in transgenic rats. These transgenic models demonstrate the feasibility of studying the function of candidate hypertension genes in transgenic animals. In the future, further refinements in transgene construction, mutation, and modification can be tested in such transgenic animal models.
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References
Jacob HJ, Lindpaintner K, Lincoln SE, Kusumi K, Bunker RK, et al (1991) Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67:213–214
Gordon JW, Ruddle FH (1983) Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Methods Enzymol 101:411–433
Ohkubo H, Kawakami H, Takumi T, Arai H, Yokota Y, et al (1990) Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes. Proc Natl Acad Sci USA 87:5153–5157
Mullins JJ, Ganten D, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344:541–544
Ganten D, Wagner J, Zeh K, Bader M, Michel JB, Paul M, Zimmermann F, Ruf P, Hilgenfeldt U, Ganten U, et al (1992) Species-specificity of renin kinetics in transgenic rats harbouring the human renin and angiotensinogen genes. Proc. Natl Acad Sci USA 89:7806–7810
Jeunemaitre X, Sourbrier F, Koteletsev YV, Lifton RP, Williams CS, et al (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180
Wagner J, Fernandez-Alfonso M, Bachmann J, Bader M, Paul M, Ganten D (1993) Update on the renin-angiotensin system, recent advances in molecular biology. Nutr Metab Cardiovasc Dis 3: 427–432
Ganten D, Takahashi S, Lindpaintner K, Mullins JJ (1991) Genetic basic of hypertension: the renin-angiotensin paradigm. Hypertension 18:108–114
Sigmund CD, Gross KW (1991) Structure, expression and regulation of the murine renin genes. Hypertension 18:446–457
Bachmann S, Peters J Engler E, Ganten D, Mullins J (1992) Transgenic rats carrying the mouse renin gene—morphological characterization of a low renin hypertension model. Kidney Int 41: 24–36
Djavidani B, Sander M, Böhm M, Kreutz R, Bader M, et al (1992) Dexamethasone suppresses development of fulminant hypertension in TGR(mREN2)27. J Hypertens 10 [Suppl 4]:S10
Lee M, Böhm M, Kim S, Bachmann S, Bachmann J, Bader M, Ganten D (1995) Differential gene expression of renin and angiotensinogen in the TGR(mREN2)27 transgenic rat. Hypertension 25:570–580
Hilgers KF, Peters J, Sommer M, Rupprecht G, Ganten D, et al (1992) Local vascular angiotensin formation in female rats harboring the mouse ren-2 gene. Hypertension 19:687–691
Bader M, Zhao Y, Sander M, Lee M, Bachmann J, Böhm M, Djavidani B, Peters J, Mullins JJ Ganten D (1994) Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats. Hypertension 19:681–686
Böhm M, Lee M, Kreutz R, Kim S, Schinke M, Wagner J, Kaling M, Wienen W, Bader M, Ganten D (1995) Angiotensinogen II receptor blockade in TGR(mREN2)27: effects on renin-angiotensin system gene expression and cardiovascular functions. J Hypertens (in press)
Peters J, Münter K, Bader M, Hackenthal E, Mullins JJ, Ganten D (1993) Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II and calcium. J Clin Invest 91:742–747
Sander M, Bader M, Djavidani B, Maser-Gluth C, Vecsei P, et al (1992) The role of the adrenal gland in the hypertensive transgenic rats TGR(mREN2)27. Endocrinology 131:807–814
Fukamizu A, Seo MS, Hatae T, Yokoyama M, Nomura T, Katsuki M, Murakami K (1989) Tissue-specific expression of the human renin gene in transgenic mice. Biochem Biophys Res Commun 165:826–832
Fukamizu A, Hatae T, Kon Y, Sugimlura M, Hasegawa T, Yokoyama M, Nomura T, Katsuki M, Murakami K (1991) Human renin in transgenic mouse kidney is localized to juxtaglomerular cells. Biochem J 278:601–603
Meiracker AH van der, Admiraal PJJ, Man in't Veld AJ, Derkx FHM, Ritsema van Eck HJ, Mulder P, Van Brummelen P, Schalekamp MADH (1990) Prolonged blood pressure reduction by orally active renin inhibitor Ro 42-5892 in essential hypertension. BMJ 301:205–210
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Wagner, J., Thiele, F. & Ganten, D. The renin-angiotensin system in transgenic rats. Pediatr Nephrol 10, 108–112 (1996). https://doi.org/10.1007/BF00863461
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DOI: https://doi.org/10.1007/BF00863461