Genetically Modified Animals

For most of the 20th century, increasing numbers of genetically defined laboratory mice have been described and incorporated into biological research; this trend has accelerated in the 21st century. Initially, research using inbred strains was limited mostly to basic genetic studies in which biochemical or visual phenotypic expression patterns were observed. With the advent of molecular genetics in the 1960s, laboratory mice developed into critical research tools in which the genomic basis of disease and mutation could be examined at the level of individual genes. By the 1970s, the prospect of intentionally modifying the murine genome by the addition of new functional DNA was at hand (Jaenisch, 1976; Jaenisch and Mintz, 1974). By the early 1980s, the persistence of microinjected laboratory-derived DNA within the cells of live-born mice (Gordon and Ruddle, 1981) and the functional expression of transgenes in mice (Brinster et al., 1981; Costantini and Lacy, 1981) were reported. Within a few years, major universities, medical schools, and pharmaceutical and biotechnology companies had created in-house transgenic mouse laboratories and genetic modification technologies had been expanded to other species. Genetically modified C. elegans, Drosophila, zebrafish, mice, and rats have been used in biomedical research for studies of basic genetics and gene function, as well as for modeling human disease. Genetically modified cattle, goats, and sheep have been used to produce proteins in milk (Schnieke et al., 1997), while genetically modified pigs have been used as large animal models of certain diseases and as potential xenotransplantation donors (Lai et al., 2002). The mouse remains the primary choice for transgenic experimentation due to the relative ease of embryo and adult manipulation and the unparalleled depth of murine genetic knowledge, although rats may have more utility for some purposes (Zheng et al., 2012). Today, genetically modified mice are produced as models of human disease, to study basic gene function and regulation, and as in vivo systems in which mammalian (and nonmammalian) genetic expression may be investigated.