The use of laboratory mice as a living system to study human disease mechanisms and test treatments.A mouse model is a laboratory mouse that has been used, often after deliberate genetic or procedural modification, to stand in for a human being in the study of a disease. Because mice are mammals, they share with us the basic architecture of organs, immune defences, hormones and metabolism, and roughly 85 percent of mouse protein-coding genes have a recognizable human counterpart. That overlap means a question that cannot ethically or practically be asked of a person — what happens if this gene is switched off, what does this drug do to a living tumour — can be asked of a mouse and the answer often carries over.
The value of the model lies less in the mouse itself than in the controlled comparison it allows. Researchers can take a group of genetically identical animals, give half of them a treatment and half a placebo, and know that any difference in outcome is caused by the treatment rather than by the accidents of individual history. They can also watch a disease from its first day, which is nearly impossible in patients who only appear in the clinic once symptoms are advanced.
Mouse models are not miniature humans, and the differences matter: mice live two to three years, have different immune signalling details, and their tumours and brains are built on a different scale. A result in mice is therefore a strong hint, not a proof, and the history of medicine contains both spectacular successes and drugs that worked beautifully in mice and failed in people.
Mice have been kept and bred in laboratories since the early twentieth century; the first inbred strain, DBA, was established by Little in 1909, and the development of targeted gene modification in mouse embryonic stem cells in the 1980s turned the mouse into the standard tool for studying gene function in a mammal.
There are three broad ways a mouse becomes a model. The first is inbreeding: decades of brother-sister mating have produced strains such as C57BL/6 in which every animal is essentially a clone, so experiments are reproducible. The second is genetic engineering, in which a chosen gene is deleted, mutated or inserted into the embryo, producing animals that carry a human disease mutation or that lack a gene whose function is being investigated. The third is direct intervention — transplanting human tumour cells, injecting a chemical, or surgically injuring a tissue — to reproduce a condition in an otherwise normal animal.
Once the model exists, the experiment is designed around measurable endpoints: survival time, tumour size, blood chemistry, behaviour in a maze, or the microscopic appearance of tissue. Because the animals are so similar to one another, even modest effects stand out against the background noise, and because generations are short, a study that would take decades in humans can be completed in months.
Mouse models are used throughout pharmaceutical development to test drug safety and efficacy before human trials, and in basic research to work out which genes and pathways drive cancer, metabolic disease, neurodegeneration and infection.
The laboratory mouse genome was sequenced in 2002, and it revealed that mice and humans have almost exactly the same set of about 20,000 protein-coding genes, differing mainly in how those genes are regulated rather than in which ones exist.