Abstract
PRIMARY hypertension is a polygenic condition in which blood pressure is enigmatically elevated; it remains a leading cause of cardiovascular disease and death due to cerebral haemorrhage, cardiac failure and kidney disease. The genes for several of the proteins involved in blood pressure homeostasis have been cloned and characterized1–8, including those of the renin–angiotensin system, which plays a central part in blood pressure control9–10. Here we describe the introduction of the mouse Ren-2 renin gene3,11–13 into the genome of the rat and demonstrate that expression of this gene causes severe hypertension. These trans-genic animals represent a model for hypertension in which the genetic basis for the disease is known. Further, as the transgenic animals do not overexpress active renin in the kidney and have low levels of active renin in their plasma, they also provide a new model for low-renin hypertension.
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References
Miyazaki, H. et al. Proc. natn. Acad. Sci. U.S.A. 81, 5999–6003 (1984).
Burnham, C. E., Hawelu-Johnson, C. L., Frank, B. M. & Lynch, K. R. Proc. natn. Acad. Sci. U.S.A. 84, 5605–5609 (1987).
Mullins, J. J. et al. EMBO J. 1, 1461–1466 (1982).
Gaillard, I., Clauser, E. & Corvol, P. DNA 8, 87–89 (1989).
Kageyama, R., Ohkubo, H. & Nakanishi, S. Biochemistry 23, 3603–3609 (1984).
Seidman, C. E., Bloch, K. D., Klein, K. A., Smith, J. A. & Seidman, J. G. Science 226, 1206–1209 (1984).
Schmale, H., Ivell, R., Breindl, M., Darmer, D. & Richter, D. EMBO J. 3, 3289–3293 (1984).
Burt, D. W. et al. in Aspartic Proteinases and their Inhibitors (ed. Kostka, V.) 355–377 (de Gruyter, Berlin, 1985).
Peach, M. Physiol. Rev. 57, 313–370 (1977).
Campbell, D. G. J. clin. Invest. 79, 1–6 (1987).
Panthier, J. J., Holm, T. & Rougeon, F. EMBO J. 1, 1417–1421 (1982).
Piccini, N., Knopf, J. L. & Gross, K. W. Cell 30, 205–213 (1982).
Field, L. J. & Gross, K. W. Proc. natn. Acad. Sci. U.S.A. 82, 6196–6200 (1985).
Mullins, J. J., Sigmund, C. D., Kane-Haas, C. & Gross, K. W. EMBO J. 8, 4065–4072 (1989).
Onoyama, K., Omae, T. & Inagami, T. Jap. Heart J. 19, 522–530 (1978).
Ekker, M., Tronik, D. & Rougeon, F. Proc. natn. Acad. Sci. U.S.A. 86, 5155–5158 (1989).
Field, L. J. et al. Molec. cell. Biol. 4, 2321–2331 (1984).
Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 132, 6–13 (1983).
Hogan, B., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1986).
Armstrong, D. T. & Opavsky, M. A. Biol. Reprod. 39, 511–518 (1988).
Rascher, W., Clough, D. & Ganten, D. in Hypertensive Mechanisms 775–801 (Schattauer, Stuttgart, 1982).
Chirgwin, J. A., Przbyla, A., McDonald, R. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).
Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).
Schelling, P., Ganten, U., Sponer, G., Unger, T. & Ganten, D. Neuroendocrinology 31, 297–308 (1980).
Hermann, K., Ganten, D., Unger, T., Bayer, C. & Lang, R. E. Clin. Chem. 34, 1046–1051 (1988).
Glorioso, N. et al. Clin. Sci. 64, 137–140 (1983).
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Mullins, J., Peters, J. & Ganten, D. Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344, 541–544 (1990). https://doi.org/10.1038/344541a0
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DOI: https://doi.org/10.1038/344541a0
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