Efforts to collect information about gene, cell, and organism function are becoming increasingly systematic and comprehensive. For example, complete genetic sequencing is being done on an ever increasing list of species. Activity levels of thousands of genes get measured simultaneously using gene array chips. As costs fall and gene array chips become more powerful gene expression gets measured in more tissue types and under more conditions (e.g. at different ages and in the presence of different kinds of illnesses). New techiniques allow quick measuring for the presence of many proteins and other compounds at the same time.
Efforts to develop lab animal strains are similarly becoming more ambitious. For many years scientists have created mouse breeds in which specific genes are deactivated. This allows scientists to more easily discover what purposes each gene serves in cells and organisms. The US National Institutes of Health are joining 2 other efforts to an ambitious effort produce gene knockout mouse strains for each of the genes found in mice.
BETHESDA, Md., Thurs., Sept. 7, 2006 – The National Institutes of Health (NIH) today awarded a set of cooperative agreements, totaling up to $52 million over five years, to launch the Knockout Mouse Project. The goal of this program is to build a comprehensive and publicly available resource of knockout mutations in the mouse genome. The knockout mice produced from this resource will be extremely useful for the study of human disease.
Some knockouts will be fatal. Embryos will fail to develop without some key genes. But discovering which genes are absolutely essential is itself quite useful knowledge. Also, once each gene has been knocked out knocking out pairs of genes in the same mouse can yield yet more useful knowledge. What is harder and done less often: Create mice that express too much of each gene. Also, genes can be created which can be turned on and off by administered drugs.
The NIH effort joins two other efforts already underway.
The NIH Knockout Mouse Project will work closely with other large-scale efforts to produce knockouts that are underway in Canada, called the North American Conditional Mouse Mutagenesis Project (NorCOMM), and in Europe, called the European Conditional Mouse Mutagenesis Program (EUCOMM). The objective of all these programs is to create a mutation in each of the approximately 20,000 protein-coding genes in the mouse genome.
"Knockout mice are powerful tools for exploring the function of genes and creating animal models of human disease. By enabling more researchers to study these knockouts, this trans-NIH initiative will accelerate our efforts to translate basic research findings into new strategies for improving human health," said NIH Director Elias A. Zerhouni, M.D. "It is exciting that so many components of NIH have joined together to support this project, and that the NIH Knockout Mouse Project will be working hand-in-hand with other international efforts. This is scientific teamwork at its best."
This ambitious project has become possible due to technological advances in methods to manipulate DNA.
Knockout mice are lines of mice in which specific genes have been completely disrupted, or "knocked out." Systematic disruption of each of the 20,000 genes in the mouse genome will allow researchers to determine the role of each gene in normal physiology and development. Even more importantly, researchers will use knockout mice to develop better models of inherited human diseases such as cancer, heart disease, neurological disorders, diabetes and obesity. Recent advances in recombinant DNA technologies, as well as completion of the mouse genome sequence, now make this project feasible.
The technological advances in tools will continue to keep happening. Advances in science do not come from a simple constant rate accumulation of knowledge. Advances in science and technology produce techniques and tools that accelerate the rate at which experiments can be done and make it possible to do new kinds of experiments and measure and manipulate more kinds of systems and phenomena.
Three quarters of the genes in mice do not yet have knockout versions.
To date, academic researchers around the world have created mouse knockouts of about 4,000 genes. In addition, a random disruption strategy has been used by the International Gene Trap Consortium to mutate 8,000 mouse genes. Due to some overlap between these efforts, about 15,000 genes remain to be knocked out in the mouse genome.
Genetic similarities between species mean the identification of purposes for mouse genes will yield insights into corresponding genes in humans and other organisms. We will learn the purposes of human genes much sooner due to the ability of scientists to knock out genes in mice.
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