Genetically Altered Rodents

Spontaneous mutations, along with those induced by chemical or physical mutagens, remain crucial as mouse and rat models. Despite this, numerous technologies for generating genetically modified animals have emerged over the years, with mice and rats standing out as premier models. Initial methods involved pronuclear microinjection of DNA fragments into one-cell embryos, resulting in approximately 10% of the offspring carrying the transgene. More recently, advanced techniques like homologous recombination in embryonic stem cells, predominantly in mice, have been developed to yield knockout or knockin animals. These approaches, while more intricate, offer even lower efficiencies in genetic modification. Lentivirus, transposons, and sperm mediated gene transfer were also available during the following years to develop new animal models with higher efficiencies, but it was not until the arrival of endonucleases and more specifically the CRISPR/Cas system that the field of genome editing grew exponentially. This technology allows the researchers to generate genetically modified mice and rats as never imagined before due to its high efficiency, low cost, and ease of design. In this chapter, we will outline both spontaneous and induced mutations, alongside the primary technologies employed for creating genetically modified mice and rats. These methodologies have been in continuous development over the past four decades. In this chapter, the term “genetically altered” (GA) rodents is utilized to encompass genetically engineered, spontaneous, and chemically induced mutations.