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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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Genre: Zeitschriftenartikel
Alternativer Titel : Proc. Natl. Acad. Sci. U. S. A.

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 Urheber:
Hansen, Jens, Autor
Floss, Thomas, Autor
Van Sloun, Petra, Autor
Fuchtbauer, Ernst-Martin, Autor
Vauti, Franz, Autor
Arnold, Hans-Hennig, Autor
Schnutgen, Frank, Autor
Wurst, Wolfgang, Autor
von Melchner, Harald, Autor
Ruiz, Patricia1, Autor
Affiliations:
1Max Planck Society, ou_persistent13              

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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2003-08-19
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: eDoc: 127827
ISI: 000184926000054
 Art des Abschluß: -

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Titel: Proceedings of the National Academy of Sciences of the United States of America
  Alternativer Titel : Proc. Natl. Acad. Sci. U. S. A.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 100 (17) Artikelnummer: - Start- / Endseite: 9918 - 9922 Identifikator: ISSN: 0027-8424