September 15, 2008 - Mice and humans, both mammals, share 90% of the genetic code. Some researchers estimate that 99% of the genes involved in human disease are also present in mice. Because mice have a shorter lifespan than humans and can have four to six litters of offspring in a year, it is possible to successfully breed mice with specific genetic features that replicate human disease.
This does not mean, however, that mouse models are easily developed. Including the work necessary to identify a target gene and the genetic manipulation and breeding of this particular mouse, it takes many years to develop a mouse model of a specific human disease.
In 1990, the U.S. government, through the Department of Energy and the National Institutes of Health (NIH), began a project to map the human genome. A genome is the complete genetic sequence of a living organism. The genome contains genes, which are encoded by DNA. Genetic variations are created when the DNA pattern within a gene is not identical between individuals. Genes control the creation and production of proteins in living things. These proteins determine how organisms look and how their systems work.
In addition to the human genome, genetic sequences of several other species were also mapped to provide comparisons and model systems in which to experiment. These included bacteria from the human digestive system, the fruit fly and the mouse.
Knowing what the DNA sequence is supposed to be in a healthy mouse, scientists can now remove part of that sequence and determine the effect of that loss on subsequent generations of the mouse. For a simplistic -- and imaginary -- example: Pretend a scientist thinks that a section of DNA on chromosome 9 is required for a protein responsible for sugar digestion. The scientist removes that section of DNA from the reproductive cells of the mouse. The altered cells are then fertilized in a test tube and baby mice are born. The researcher then determines whether those baby mice can or cannot digest sugar. That’s how they know whether the sequence they suspect is the correct genetic sequence. Moving that simple example forward, scientists are able to “knock-out” the sequence that they suspect might be involved in a disease and study the effect on the mice.
This is one of the techniques used to genetically alter a mouse and create a model for an existing human disease. Mice bred with the missing DNA are observed and tested for the characteristics of the human disease being studied. Once scientists are satisfied that the mouse strain is consistently showing the disease, colonies of that mouse strain are bred for additional study.
Mouse models offer scientists a living system to understand what causes disease, how it might affect humans and to develop solutions that might stop or prevent disease progress.