Published online 5 December 2002 | Nature | doi:10.1038/news021202-10


Mice make medical history

The scientific credentials of the lab mouse are impressive.

Mus musculus: one of scientists' greatest allies.Mus musculus: one of scientists' greatest allies.© alamy

A dog may be man's best friend but the humble mouse, Mus musculus, is certainly our greatest ally. With today's publication of its genetic sequence, it is time to tip hats to the animal that has shaped our scientific and medical landscape.

An army of mice, perhaps 25 million strong, each day help researchers worldwide to study and devise treatments for human ailments such as cancer, heart disease, AIDS and malaria. Mice are helping to unravel mysteries of biology, such as why we grow old. Discoveries made using mice have netted 17 Nobel Prizes, and more will undoubtedly follow.

The animal's worth stems largely from the fact that mice, like us, are mammals and share around 80% of our genes. And because they breed rapidly and happily in captivity, inheritance of characteristics can be easily studied.

These attributes make the mouse "the perfect model organism" for human biology, says Rick Woychik, director of the Jackson Laboratory in Bar Harbor, Maine, one of the world's pre-eminent mouse research labs.

Showing the strain

The rodent's esteemed scientific career began in around 1900 on a farm in Granby, Massachusetts. Mouse-fancier Abbie Lathrop turned her hobby into a business by selling some of the animals she bred to researchers at the nearby Massachusetts Institute of Technology, pursuing the new science of genetics.

In 1909 one such scientist, called Clarence Cook Little, became the surrogate father of the modern lab mouse. Little, who went on to found the Jackson Laboratory, mated closely related mice for generation after generation, creating the first inbred strain.

In 1909, Clarence Cook Little created the first inbred mouse strain.In 1909, Clarence Cook Little created the first inbred mouse strain.© Jackson Laboratory.

Inbred mice are ideal for studying the biological effects of a genetic mutation or an environmental influence such as diet. Such effects are obvious because these mice are almost genetically identical. They gave researchers studying disease or inheritance a simple genetic canvas on which to work.

Natural mutants from inbred strains that are prone to obesity, cancer or defects in their immune system soon began to emerge, fuelling a deeper understanding of disease and biology. A chance discovery in the early 1980s, for example, yielded the severe combined immune deficiency (SCID) mouse, which lacks a working immune system. The strain offers a unique opportunity to probe how the body normally defends itself from infection.

Many modern researchers still study strains which are naturally obese or diabetic. Using DNA-sequencing techniques to compare these mice with healthy ones, the many genes and environmental factors that contribute to these disorders are becoming clearer.

It's a knockout

In 1980, mouse genetics underwent something of a revolution - with the advent of techniques that allow genetic modification. These experiments culminated in the creation of the first 'knockout' mice, from which a particular gene of interest had been removed. "It allowed us to define exactly what a gene was doing in the life of an organism," recalls Mario Capecchi, a knockout-mouse pioneer at the University of Utah in Salt Lake City.

“It allowed us to define exactly what a gene was doing in the life of an organism”

Mario Capecchi
University of Utah

These and related techniques have produced invaluable mouse models of human illnesses ranging from heart disease to cystic fibrosis and Alzheimer's. For example, a knockout mouse that lacks a working ion pump in cells lining the lung and gut, has advanced research into the fatal lung disease cystic fibrosis.

Nowadays, more advanced genetic engineering is helping scientists to understand exactly what a gene is doing in the body. For example, researchers have inserted specific genes that encode elements of the human immune system into SCID mice. This allows pieces of man's vastly complex immune system to be studied one at a time.

Antibody factories

Genetics aside, mice have given rise to important diagnostic tools and treatments. In 1975 researchers at Cambridge University in England fused immortal cells derived from a cancer-prone mutant mouse with immune-system cells called B lymphocytes. The resulting cells, called hybridomas, could be used to produce a never-ending supply of disease-fighting molecules called antibodies.

Antibody-based drugs are already available to fight breast cancer, leukaemia and arthritis.Antibody-based drugs are already available to fight breast cancer, leukaemia and arthritis.© alamy

Made-to-order versions called humanized monoclonal antibodies "have been absolutely dramatic in terms of their uses", says field pioneer Greg Winter of the UK Medical Research Council's Laboratory of Molecular Biology in Cambridge. They can be manufactured to home in on almost any molecule, such as a protein on a cancer cell, by priming the lymphocytes to that molecule.

Some 20% of all candidate drugs now under development are based on monoclonal antibodies. An antibody targeted at a cancer cell, for example, can be used to alert the body's immune system to the tumour and encourage its destruction.

Antibody-based drugs are already available to fight breast cancer, leukaemia and arthritis. "They are a beautiful way to get value out of what we've learned about the mouse," says Winter. 

University of Utah Salt Lake City