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Current issues in mouse genome engineering

Abstract

The mouse is the foremost vertebrate experimental model because its genome can be precisely and variously engineered. Now that the mouse genome has been sequenced and annotated, the task of mutating each gene is feasible, and an international cooperation is providing mutated embryonic stem cells and mice as readily available resources. Because these resources will change biomedical research, decisions about their nature will have far-reaching effects. It is therefore timely to consider topical issues for mouse genome engineering, such as the background genotype; homologous, site-specific and transpositional recombination; conditional mutagenesis; RNA-mediated interference; and functional genomics with embryonic stem cells.

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Figure 1: Scheme for rapidly constructing optimized targeting vectors.
Figure 2: Strategies to impose asymmetry onto Cre recombination.
Figure 3: Strategies to create homozygosity in ES cells.
Figure 4: Engineering above 10 kb.

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Acknowledgements

We thank H. von Melchner, B. Skarnes, A. Smith, G. Testa and G. Yancopoulos for discussions. This work was supported by funding from the Sixth Research Framework Programme of the European Union, Project FunGenES and the VW Program on Conditional Mutagenesis.

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Correspondence to A Francis Stewart.

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A.F.S. is a shareholder in GeneBridges GmbH (DNA Engineering) and a consultant to SAB member Artemis Pharmaceuticals GmbH (Mouse Engineering).

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Glaser, S., Anastassiadis, K. & Stewart, A. Current issues in mouse genome engineering. Nat Genet 37, 1187–1193 (2005). https://doi.org/10.1038/ng1668

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