Transgenic Mice in Developmental Toxicology
Recent advances in molecular biology and embryology are being utilized for experiments in mammalian genetics and toxicology. Some of the most important developments are based on the generation of transgenic mice, which are animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Originally, pronuclear microinjection or retroviral infection of early-stage embryos was used to generate transgenic mice, and the integration of the exogenous DNA constructs occurred randomly throughout the host genome (reviewed by Palmiter and Brinster, 1986). In the past several years, mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes (reviewed by Capecchi, 1989; Frohman and Martin, 1989). Most important, the majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, it will be the objective of this review to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.
KeywordsToxicity Recombination Toxicology
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