TRANSGENIC ANIMALS AS NEW APPROACHES IN PHARMACOLOGICAL STUDIES

Transgenic animals are becoming useful tools for pharmacological studi es. The use of transgenic technology raises two types of questions, '' How are transgenic animals made?'' and ''What types of pharmacological questions can be answered using transgenic technologies?'' Answers to these questions are discussed in this review. The production of anima ls with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromo somes. The second strategy is to select particular genetic loci for si te-specific changes. There are two well-established procedures for sim ple introduction of DNA into an animal genome, pronuclear DNA injectio n and transduction using a retrovirus. In contrast, methods for target ing specific DNA sequences to definite sites in the chromosomes are ev olving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacologi cal studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology.