A large-scale, gene-driven mutagenesis approach for the functional analysis of 
the mouse genome

Hansen, Jens; Floss, Thomas; Van Sloun, Petra; Fuchtbauer, Ernst-Martin; Vauti, Franz; Arnold, Hans-Hennig; Schnutgen, Frank; Wurst, Wolfgang; von Melchner, Harald; Ruiz, Patricia

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A large-scale, gene-driven mutagenesis approach for the functional analysis of the mouse genome

Hansen, J., Floss, T., Van Sloun, P., Fuchtbauer, E.-M., Vauti, F., Arnold, H.-H., et al. (2003). A large-scale, gene-driven mutagenesis approach for the functional analysis of the mouse genome. Proceedings of the National Academy of Sciences of the United States of America, 100(17), 9918-9922.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-89CC-E Version Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-89CD-C

Genre: Journal Article

Alternative Title : Proc. Natl. Acad. Sci. U. S. A.

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Creators:
Hansen, Jens, Author
Floss, Thomas, Author
Van Sloun, Petra, Author
Fuchtbauer, Ernst-Martin, Author
Vauti, Franz, Author
Arnold, Hans-Hennig, Author
Schnutgen, Frank, Author
Wurst, Wolfgang, Author
von Melchner, Harald, Author
Ruiz, Patricia¹, Author

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1Max Planck Society, ou_persistent13

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Abstract: A major challenge of the postgenomic era is the functional characterization of every single gene within the mammalian genome. In an effort to address this challenge, we assembled a collection of mutations in mouse embryonic stem (ES) cells, which is the largest publicly accessible collection of such mutations to date. Using four different gene-trap vectors, we generated 5,142 sequences adjacent to the gene-trap integration sites (gene-trap sequence tags; http://genetrap.de) from >11,000 ES cell clones. Although most of the gene-trap vector insertions occurred randomly throughout the genome, we found both vector-independent and vector-specific integration "hot spots." Because >50% of the hot spots were vector-specific, we conclude that the most effective way to saturate the mouse genome with gene-trap insertions is by using a combination of gene-trap vectors. When a random sample of gene-trap integrations was passaged to the germ line, 59% (17 of 29) produced an observable phenotype in transgenic mice, a frequency similar to that achieved by conventional gene targeting. Thus, gene trapping allows a large-scale and cost-effective production of ES cell clones with mutations distributed throughout the genome, a resource likely to accelerate genome annotation and the in vivo modeling of human disease.

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Language(s): eng - English

Dates: Date issued: 2003-08-19

Publication Status: Issued

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Identifiers: eDoc: 127827
ISI: 000184926000054

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Title: Proceedings of the National Academy of Sciences of the United States of America

Alternative Title : Proc. Natl. Acad. Sci. U. S. A.

Source Genre: Journal

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Pages: - Volume / Issue: 100 (17) Sequence Number: - Start / End Page: 9918 - 9922 Identifier: ISSN: 0027-8424