Transgenic animals in hypertension research. New approaches to old questions.

Techniques for introducing eukaryotic DNA sequences into the genomes of fertilized mammalian embryos have been available for more than 10 years. The production of transgenic animals (primarily mice) from these embryos has provided a valuable tool for the study of molecular, cellular, and whole animal physiology in the recipient. The power of the technique derives from the fact that the expression of the transgene can be followed developmentally for extended periods of time, in most cases for the entire lifetime of the recipient, in a setting that minimally perturbs the remainder of the animal's genome. In addition, because the transgene is incorporated into the recipient's germ line as well as somatic cells, it is transmitted to its offspring with a high degree of fidelity, thereby allowing for detailed molecular or physiological studies as the strain is propagated over subsequent generations. To date, transgenic animals have been used to address a variety of different biological questions with considerable success. They have been used to study the details of tissue-specific gene expression and have accurately identified cis-acting enhancer sequences responsible for conferring this specificity on target genes. They have also been used to locate cis-acting DNA elements that confer sensitivity to environmental stimuli (e.g., glucocorticoid or heavy metals) on contiguous coding sequences. They have been used to determine the effects of protein (e.g., hormone) overproduction in transgene-bearing animals and, in some instances, to replace a defective gene in the recipient. Chimeric transgenes linking tissue-specific regulatory elements to oncogene coding sequences have been used to foster the development of malignancies in selected tissues, in some cases as a prelude to establishing a transformed cell line retaining the phenotype of the targeted cell. Finally, the transgenic approach has been used to eliminate cells of a particular phenotypic lineage from the recipient animals. This has been accomplished by linking cell-specific or tissue-specific regulatory elements either to toxins, interferon, or