Manipulating the Rat Embryo: Genetic and Stem Cell–Based Technologies for Physiological Research

) have been invaluable to biomedical research and are well-suited for physiological analyses. Nevertheless, technical challenges in embryo and genetic manipulation have historically hindered the generation of genetically modified rats, thereby limiting their use for in vivo functional genetic studies. Recent advances, including genome editing and pluripotent/germline stem cell technologies, have substantially expanded rat genetic engineering. This review summarizes the historical background and recent advances in rat embryo manipulation and highlights the rapid development of genetic tools in rats, now catching up with those available in mice. These advances provide an opportunity to reassess the value of rats as experimental models. Furthermore, the combined use of mice and rats, exemplified by interspecific chimeras and comparative studies, offers new insights into conserved and species-specific physiological mechanisms across mammals.