Genetic manipulation of the mouse genome
Perhaps the most important advantage to using the mouse for biomedical research is the ability to experimentally manipulate the mouse genome. Genes can be injected directly into the fertilized egg of a mouse creating what is known as a transgenic animal. This approach allowed scientists to create a new set of models and experimental tools based on the manipulation of specific genes thought to be important in the pathology of certain diseases.
Subsequently, scientists developed techniques that allowed them to specifically target genes within the mouse genome—so-called “knockouts”—that further enhanced their biological toolkit. The foundation for this work was laid by the pioneering work of Leroy Stevens at The Jackson Laboratory, culminating in the discovery that pluripotent embryonic stem (ES) cells could be grown in culture and that mouse genes could be altered in such cells by homologous recombination or targeting. Thousands of mouse genes have been targeted in this fashion and the new Knockout Mouse Project (KOMP) initiated by the NIH, together with efforts in Canada and Europe, has the ambitious goal of knocking out all of the genes in the mouse genome within the next few years. This will provide a comprehensive resource of unparalleled value for biologists seeking to understand the genetic basis of mammalian biology and disease progression.
And the toolkit continues to expand. The same gene targeting technology used to create knockouts can be employed to replace mouse genes with genes that encode fluorescent proteins into the mouse genome providing researchers with powerful tools to image and track specific cell types. Mouse genes can be replaced with human genes to study gene function or to produce more human-like model systems in the mouse. New technologies allow scientists to not only knock out genes of interest, but to do so in a specific tissue at a specific time, refining their ability to ask crucial questions. As these tools continue to be developed, scientists will expand their ability to not only accurately model human disease, but to directly test their theories using the mouse.
