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A knockout resource for mouse genetics
Date:6/15/2011

r mouse mutagenesis - to provide resources efficiently and consistently and to release them freely. Previously attempted strategies to develop mouse models on a large scale suffered the twin disadvantages of not producing precise genetic changes and favouring only the genes that were active during the experiment, leaving the remainder unaltered.

The present work solves these problems. The team exploited a system called homologous recombination within mouse embryonic stem cells, which can deliver very precise alteration of any gene in the genome. It is founded on choosing the correct recombinant DNA molecules (vectors) to target genes efficiently.

However, some genes are essential to life of the cell or organism: disruption of these might cause the cell to die and so the mutation would be 'lost' from the project. Crucially, to ensure that all genes can be disrupted, the team developed DNA vectors that create a mutation only when required: gene targeted by the mutation can be identified, but the mutation activated only when it is to be studied.

But in the essential step to realize its ambitions of a comprehensive, freely available resource, the team designed and delivered a 'pipeline' that systematically designs and constructs the vectors, and efficiently introduces the engineered DNA molecules into the mouse embryonic stem cell line developed specifically for these projects.

Finally, by employing a modular approach to the vector design, a number of other valuable resources are created en route to the generation of targeted ES cells: the paper reports that the consortium had produced vectors for more than half of the genes in the mouse genome. All of these outputs are being made available to the mouse research community through the consortium's web portal at http://www.knockoutmouse.org/

"We are producing mutations in embryonic stem cells with greater efficiency and speed than w
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Contact: Don Powell
press.office@sanger.ac.uk
44-122-349-6928
Wellcome Trust Sanger Institute
Source:Eurekalert

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