Super models

Evolution may have led to distinct appearances and biologies for yeast, worms, mice and humans, but it also left many essential systems alone. Fundamental cellular mechanisms are remarkably similar from the lowliest single-celled microbe to the most advanced mammal, and so model organisms provide valuable systems in which to explore key gene function. Underpinned by genome sequencing, the Sanger Institute’s already well-established studies of yeast and the nematode worm are now being augmented by the most powerful model for understanding human biology and disease - the mouse.

A mouse in the house

Mice and humans diverged from a common ancestor about 140 million years ago, yet many aspects of mammalian physiology have not changed significantly in these lineages. The mouse is a particularly attractive organism for investigating gene function because many aspects of early development, basic organ systems, skeleton and reproductive systems are similar. Moreover, the genomes of mice and humans are quite conserved - every human gene has a mouse counterpart, and 85 per cent of their gene sequences are shared - so discoveries in one species are often informative to the other.

"There are lots of bridges that we can build between the species," says Allan Bradley. "There are many examples of human inherited diseases that can be mimicked in mice by knocking out a gene. The mouse is surrogate to human studies."

The isolation of embryonic stem cells and the demonstration that these cells could transmit modified genes into the mouse germ line - thus being passed onto the next generation - signalled the beginning of a revolution in mouse genetics. Using this technology, thousands of mouse strains with specific mutations have been generated over the last ten years. "Mice bring an aspect of what we call manipulative genetics that doesn’t exist in any other species," says Dr Bradley. "Everything you can do in yeast - knock out a gene or change an amino acid - you can do in mice. It’s an extremely powerful system."

Over the next five years, the Institute will initiate studies of mouse models of human disease, complementing work in other top genome research centres across the world and other biomedical centres in the UK. These studies will be underpinned by the mouse genome, which is being sequenced by an international consortium; the Sanger Institute is responsible for sequencing 20 per cent of the genome, and the project is due for completion in 2005.

"The mouse has 30 000 or so genes, but only about 10 per cent of these genes have been looked at so far," says Dr Bradley. "There is a huge amount of work to be done."

See also

• The Human Genome Project: Information on the project and the key issues

External links

• The Mouse Genome Project at the Sanger Institute