Pediatric Nephrology

, Volume 10, Issue 1, pp 108–112 | Cite as

The renin-angiotensin system in transgenic rats

  • Jürgen Wagner
  • Felix Thiele
  • Detlev Ganten
Invited Review


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.

Key words

Transgenic rat Transgene Renin Angiotensinogen Cardiovascular system Pharmacology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    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 67:213–214Google Scholar
  2. 2.
    Gordon JW, Ruddle FH (1983) Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Methods Enzymol 101:411–433Google Scholar
  3. 3.
    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 87:5153–5157Google Scholar
  4. 4.
    Mullins JJ, Ganten D, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344:541–544Google Scholar
  5. 5.
    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 89:7806–7810Google Scholar
  6. 6.
    Jeunemaitre X, Sourbrier F, Koteletsev YV, Lifton RP, Williams CS, et al (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180Google Scholar
  7. 7.
    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: 427–432Google Scholar
  8. 8.
    Ganten D, Takahashi S, Lindpaintner K, Mullins JJ (1991) Genetic basic of hypertension: the renin-angiotensin paradigm. Hypertension 18:108–114Google Scholar
  9. 9.
    Sigmund CD, Gross KW (1991) Structure, expression and regulation of the murine renin genes. Hypertension 18:446–457Google Scholar
  10. 10.
    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: 24–36Google Scholar
  11. 11.
    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]:S10Google Scholar
  12. 12.
    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 25:570–580Google Scholar
  13. 13.
    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 19:687–691Google Scholar
  14. 14.
    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 19:681–686Google Scholar
  15. 15.
    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)Google Scholar
  16. 16.
    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 91:742–747Google Scholar
  17. 17.
    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 131:807–814Google Scholar
  18. 18.
    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 165:826–832Google Scholar
  19. 19.
    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 278:601–603Google Scholar
  20. 20.
    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 301:205–210Google Scholar

Copyright information

© IPNA 1996

Authors and Affiliations

  • Jürgen Wagner
    • 1
  • Felix Thiele
    • 1
  • Detlev Ganten
    • 1
  1. 1.Max Delbrück Centrum for Molecular MedicineBerlinGermany

Personalised recommendations