Knockout mice library starts
Watch the corks fly! A global research initiative aimed at generating a comprehensive and public collection of knockout mice has gained support. Does a dream come true, asks Rafael Flores.
The European Commission, US National Institutes of Health and Genome Canada have agreed to build up an extensive knockout mice library. This research effort will be the largest worldwide after the Human Genome Project.
The aim is to coordinate efforts to create a repository of mice containing a zero mutation in every gene in the mouse genome and to make the repository freely available to the entire scientific community. Such a library of mutant mice has been the dream of the human genomic community during recent years because it is an ideal means to determine gene functions. Since mice are genetically very similar to humans, one hopes to elucidate the genetic basis of disease development.
Sounds great, doesn't it? However, it is not all that wonderful. Like a curse, when knockout mice are around everything becomes so embarrassing that such a task may be considered anything but easy. Just for starters, the US-NIH KOMP project disagrees with its Canadian and European partners on the methods of how to generate the mutants. Basically, the goal of the European and Canadian programs is to generate 20.000 conditional mutations (12.000 conditional gene-trap mutations and 8.000 conditional targeted mutations) in ES cells, all in strain 129. The NIH deputies, however, think that besides the undeniable advantages, conditional mutations in mice could lead to genetic artefacts. That's why they are going to generate null alleles using a high utility reporter insertion. For that purpose NIH researchers will use C57BL/6 mice, the most widely used strain and the one for which the complete genome sequence has been made available. Their intention is to focus part of their effort on compiling together the high priority knockout mutants already available, which they estimate to be about 10.000 (although, at presend, only 3000-4000 of these are publicly available). To cover the remaining genes in the mouse genome they will have to create a minimum of 10.000 more mutants. At best, this procedure will not only incur extra costs in resources and time but will also create a diversification of the collection that, hopefully, will ameliorate the repository.
The project is the institutional response to an initiative taken by a consortium of outstanding scientists in the field of human genomics.
The agreement unites three projects: The European Conditional Mouse Mutagenesis Program (EUCOMM) funded with €13 million by the European Commission, the North American Conditional Mouse Mutagenesis Program (NorCOMM) funded with $13.5 million by Canada and the Knockout Mouse Project (KOMP) financed by the US-NIH with $50 million for five years.
This task should be warmly welcomed by the scientific community for various reasons. Generating knockout mice is certainly a complex job, far from being easy - as many researches having tried it will agree. Only a few groups around the world can boast the facilities and the means to afford specialised personnel to perform this activity. Ordering mutants from some specialised companies can be very expensive. Getting published knockouts from other researchers often turns out to be a difficult venture.
What appears on the surface to be a simple transaction often causes a lot of ineffective extra work due to insufficient coordination between labs and scanty communication. Hence, what began as the one time graces the knockout mice have transformed into the groans in the science labs and so, over the last decade, knockout mice have become one of the most likely subjects to turn into a top scientific nightmare! That is precisely what the announced international initiative intends to reduce. I certainly hope that this intention can be realised.
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