1-An ambitious effort to identify the function of every gene in the mouse genome looks set to provide scientists with the ultimate mouse model of human disease.
2-The International Mouse Phenotyping Consortium (IMPC) has yet to find all of the US$900 million it needs to complete its task over the next decade. But at a meeting on mouse models of human diseases in London, where the project was unveiled last week, scientists announced a commitment of $110 million from the US National Institutes of Health (NIH) in Bethesda, Maryland over the next five years.
3-The IMPC aims to take mice of identical genetic background and to create viable strains in which one of the 20,000 or so genes in the mouse genome is knocked out, or deactivated. The knockout strains will then be put through rigorous, systematic phenotypic screens, which will check for physical and behavioural differences. The information will be stored in a purpose-built, open-access database.
4-Scientists would, for example, be able to turn to the database to learn more about an unfamiliar gene signalled in a genome-wide association study in humans as being possibly relevant to a particular disease. Making the mutant animal and phenotyping it in a lab could take three years.
5-But the launch of the visionary programme comes at a time of global financial crisis and may have trouble finding additional funders. Some scientists had looked to the European Commission, which sponsored the meeting and has spent close to €250 million (US$305 million) over the past ten years to pioneer systematic phenotyping of mice, and to generate mutant mice. But Leszek Borysiewicz, chief executive of the UK Medical Research Council (MRC) in London, warned at the meeting that the commission's politicians would need a lot of con vincing that mouse genomics was more deserving of funds than other scientific projects.
6-The mouse genome was the first to be sequenced after the human because of its importance as a laboratory model. "But it soon became clear that it is impossible to predict function directly from sequence," says Paul Schofield, a geneticist at the University of Cambridge, UK, who helped to organize the meeting. "Also, there are black holes in the genomes where we simply don't know what the genes do — the mouse phenotype database would give us traction."
7-Mouse 'clinics' have sprung up around the world to screen mutant mice for crude phenotypes — such as heart defects — and to perform secondary screens to investigate the changes in more detail. But it is already clear that even this is not enough. Gene expression, and the resultant phenotype, are profoundly influenced by environment, and many of these mice are raised in a stressed environment for the purposes of experiments — for example, being fed high-fat diets or subjected to infection. Much more will be learnt by comparing phenotype screens carried out on mutant mice raised in a normal environment, say project scientists.
8-"The IMPC sounds expensive but it is not compared with other genomic resources," adds Moore. "The database only needs to help industry to develop a handful of multibillion-dollar blockbuster drugs and it will have paid for itself."
From- Nature News
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