With the completion of the human genome sequence and those of other mammals, the next challenge is to assign function to the many newly identified genes. Genetic studies in the mouse have yielded the most information on the functions of mammalian genes in physiology and disease processes. Spontaneous or induced mutations that give rise to observable traits (phenotypes) provide important clues to the functions of the mutated genes.The most effective application of this principal has been the deliberate engineering of defined genetic modifications in mice by homologous recombination in mouse embryonic stem (ES) cells.
Most modifications are designed to inactivate gene function and are commonly referred to as knockout (KO) or null mutations. ES cells carrying a KO mutation can be introduced into embryos, where they will contribute to the tissues of the developing mouse. If the genetically modified ES cells contribute to germ cell development, the engineered mutation can be transmitted to subsequent generations to establish a line of mutant mice that can be studied to determine the effects of the loss of the normal gene's function.
Directed gene modification in ES cells has been applied to thousands of mouse genes and has proven to be a powerful tool for the elucidation of gene function, but the conventional methods require highly trained scientists to perform multiple time-consuming and labor-intensive procedures that can take 12 to 18 months just to obtain the modified ES cells.
To unlock the full potential of targeted genetic modification for the elucidation of gene function, we re-engineered the process of making a genetically modified mouse by developing improvements in each step from allele design to mouse production. Our innovative technologies have transformed mouse research and greatly expanded its horizons.
