TRANSGENIC ANIMAL-MODELS FOR HYPERTENSION RESEARCH

Experimental hypertension research has advanced primarily through phar macologic and physiologic experiments, as well as classic breeding stu dies in whole animal models. Information obtained from these intervent ions has recently been enhanced by the identification of candidate gen es, which could be contributing to the pathophysiology of hypertension . Transgenic techniques have a significant impact in this context by l inking the information derived front the genetic studies to the hypert ensive phenotype. Most commonly, transgenic experiments are carried ou t to add specific gene sequences, and this is routinely performed by d irect microinjection of DNA consisting of regulatory and coding sequen ces into the pronucleus of fertilized oocytes. Homologous or heterolog ous regulatory sequences are responsible for targeting the expression of genes to tissues and cells. The effect of this ''gene addition'' on the phenotype can then be analyzed by using the methodologic arsenal of cardiovascular physiology and pharmacology. The majority of transge nic studies have been carried out in mice, but recent efforts have als o focused on other species, such as the rat. In addition, new techniqu es are available, which include the use of homologous recombination in embryonic stem cells to perform ''gene-deletion'' studies or the appl ication of cell-specific promoters to target and ''knockout'' gene exp ression in specific tissues.