Mice and men are genetically far further apart than was previously thought, calling into question the important role the rodents play in medical research.
A study has found that while mice and humans share many protein-coding genes, the way their genes are regulated is often very different.
US scientists were surprised to find that gene activity diverged wildly between the two species in some key biological pathways.
The finding may help explain why more than 90 per cent of new medicines that pass animal tests then fail in human trials.
Laboratory mice have been a pillar of medical research for more than a century, being used by scientists investigating everything from social behaviour to obesity.
Bing Ren, from the University of California at San Diego, who co-led the new research, said: “The assumption has long been that whatever was discovered in the mouse would likely be true in humans too, but the idea has never been systematically evaluated and assessed.
The finding may help explain why more than 90 per cent of new medicines that pass animal tests then fail in human trials
“We know now that this assumption is not entirely true. There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans. The differences are not random. They are clustered along certain pathways, such as in genes regulating the immune system.”
The research, published in the journal Nature, is part of the Encode (Encyclopedia of DNA Elements) project comparing functional parts of the human and mouse genome.
Only half of human and mouse DNA match compared with 96 per cent of human and chimpanzee DNA.
Mice and humans do share some 70 per cent of the same protein-coding DNA sequences, the genes that provide the instructions to build a living organism. But these make up only 1.5 per cent of the DNA in each species.
While the vast majority of DNA does not code for proteins, some of what used to be known as ‘junk’ DNA plays an active role in regulating gene activity. It is these non-coding ‘regulatory elements’ that vary so much in mice and humans.
The scientists analysed 100 mouse cell types and tissues including brain, heart, blood, kidney, liver and skin, and found that in some cases regulatory pathways in each species had evolved quite differently.
For example, gene activity patterns in the mouse brain were more similar to those of the mouse intestine than the human brain.
Co-author Michael Beer, from Johns Hopkins University School of Medicine, said: “Most of the differences between mice and humans come from regulation of gene activity, not from genes themselves. Because mice are an important model for human biology, we have to understand these differences to better interpret our results.”
He added: “It is becoming clearer that most human disorders, from diabetes to attention deficit hyperactivity disorder to Parkinson’s disease, actually stem from off-kilter gene regulation.”
Katy Taylor, head of science at the British Union for the Abolition of Vivisection (BUAV) said: “Instead of stubbornly forging ahead with ever greater amounts of research involving mice as replacements for humans, we should instead be looking ahead to what can be achieved using technologically advanced human-specific clinical and in vitro research.
“Only by studying human cells, tissues, and real people, can true − and humane - medical progress be made.”
Isobel Hutchinson, from Animal Aid, said: “This important new study points to the folly of using GM (genetically modified) mice as surrogate humans, given the fundamental differences in the way genes are regulated in people and mice.
“It is an area of global research that is responsible for inflicting appalling suffering on millions of animals.
“The findings of this latest study should act as an urgent wake-up call for the scientific community to rethink its current obsession with the cruel and fruitless enterprise of GM mouse research.”