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IT鈥橲 been called the 鈥淩osetta stone鈥� that will unlock the secrets of the human genome. And now it has been officially unveiled.

The long-awaited draft sequence of the mouse genome was published this week in Nature, just two years after a global Mouse Genome Consortium of publicly funded institutes set to work to unravel the code of 鈥淏lack 6鈥�, a common lab strain. Private rival Celera said it assembled its mouse genome in April 2001, but so far it has published details of only one chromosome.

Gene sleuths have coveted the mouse genome as an instant reference manual. Although the human genome has already been sequenced, it鈥檚 another matter to work out which pieces of the sequence are genes, and what all those genes are for.

That鈥檚 where mice come in. It鈥檚 not that mice are particularly close relatives 鈥� we parted evolutionary ways with them 75 million years ago. But they are probably the most studied creatures in the world, and have long been used to test potential drugs. The standard refrain when researchers announce promising results is 鈥測et more mice cured鈥�.

Natural mutations in mice have already enabled scientists to identify the function of many mouse genes and their human equivalents. Having the entire mouse genome will make this much easier. It also makes it possible to create deliberate mutations, to see what effect they have. That is not the kind of experiment you can do with people, but often a disease caused by a gene mutation in mice corresponds with a disease in humans. Finding out which mutations do what can provide vital clues to how human diseases develop and, sometimes, how to treat them.

Of course, with so much work being done on mice, the key question is: just how similar to us are they? Computer analyses suggest that like us, mice have around 30,000 genes, although some think both counts are too low.

Most remarkably, the results published this week suggest that we have only 300 genes that mice don鈥檛, and vice versa. For every one of the rest of our genes 鈥� 99 per cent of the total 鈥� one or more related genes have been found in mice.

The only major differences appear in genes for immunity, reproduction, detoxification and, surprise surprise, smelling. 鈥淭hey have a vast number of differences in their olfactory receptors,鈥� says Chris Ponting of the Medical Research Council鈥檚 Functional Genetics Unit at Oxford University, who has been studying the differences. Mice rely on their sense of smell for mating as well as finding food, he says.

Female mice also have an larger repertoire of reproduction genes compared with us. Whereas women make a single pregnancy-specific hormone, prolactin, the genome scan suggests that mice make around 20.

Early comparisons have also revealed fairly substantial differences in the liver 鈥渄etox鈥� genes. These code for enzymes called cytochrome P450s, which are needed to break down poisons, toxins and drugs. There are various types of these enzymes, and each is responsible for breaking down a different class of molecules. It turns out that mice have 84 different detox genes, whereas we have just 63.

That is probably because mice encounter more toxins, says Peer Bork, whose team at the European Molecular Biology Laboratory in Heidelberg, Germany, did the analysis of the detox genes. The next step is to find out exactly how each enzyme works, which chemicals they break down and how they work in tandem. That could help us understand just how relevant mouse studies are to humans. 鈥淚t doesn鈥檛 invalidate previous toxicological findings,鈥� Bork says. 鈥淏ut with the genome, we can evaluate any 鈥榝ailure factors鈥� more accurately.鈥�

Ultimately, it may be possible to 鈥渉umanise鈥� lab mice through genetic engineering, so that they metabolise drugs the way we do. But it would take 鈥渁 hell of a lot of work鈥�, Bork says.

Meanwhile, other comparisons of the two genomes are helping uncover why inheriting three copies of chromosome 21, which occurs in 1 in 700 births, causes Down鈥檚 syndrome. A tri-institute team led by Stylianos Antonarakis at the University of Geneva Medical School has identified 161 genes in mice related to the 178 found so far on human chromosome 21, the smallest of our chromosomes.

The team compiled an 鈥渁tlas鈥� of mouse body tissues showing when and where each of the 161 genes were activated during embryonic and adult development. It revealed genes potentially linked to all the main manifestations of Down鈥檚, including defective heart valves, facial and finger abnormalities and mental retardation.

But understanding disease is not the only goal of the mouse genome project. Having both genomes will also help biologists better understand how genes work at the most basic level. The mouse genome has already thrown up one puzzle that reveals just how little we know. Many small segments of the mouse and human genomes are nearly identical, or 鈥渃onserved鈥�, which suggests they do something important, and yet they do not appear to consist of genes coding for proteins.

For example, Antonarakis found over 3000 chunks of human chromosome 21, about 5 per cent, that were identical to ones on the mouse counterpart. But only a third of these conserved regions corresponded with known genes. The rest must serve unknown functions. 鈥淓ach chunk is unique, so they鈥檙e all doing something different,鈥� says Antonarakis. They could help regulate expression of genes on this and other chromosomes, he says, or they may maintain the structure of chromosomes.

The regulatory regions of the genome that help turn genes on and off have been notoriously hard to identify, adds Wayne Frankel of the Jackson Laboratory in Bar Harbor, Maine. Now everyone is going to look in the conserved regions to see if they can find these gene switches, he says.

Although pleased with their curtain-raising work, researchers in the consortium, which includes the Sanger Center in Cambridge and the Whitehead Institute in Boston, say that it is just the beginning. And there are still a few loose ends: the mouse DNA came from females, for instance, so the Y chromosome has yet to be sequenced.

Already some are saying we need to sequence yet more genomes to settle questions about discrepancies between us and mice. The pufferfish鈥檚 compact genome was revealed earlier this year (New Scientist, 3 August, p 19), but it is a very distant relative. Next up could be the dog, cat, chicken and, of course, the chimpanzee. With the pace hotting up as each new sequence is published, there may not be long to wait.