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| ID:
127827.0,
MPI für molekulare Genetik / Department of Vertebrate Genomics |
| A large-scale, gene-driven mutagenesis approach for the functional analysis of the mouse genome |
| Authors: | Hansen, Jens; Floss, Thomas; Van Sloun, Petra; Fuchtbauer, Ernst-Martin; Vauti, Franz; Arnold, Hans-Hennig; Schnutgen, Frank; Wurst, Wolfgang; von Melchner, Harald; Ruiz, Patricia | | Language: | English | | Date of Publication (YYYY-MM-DD): | 2003-08-19 | | Title of Journal: | Proceedings of the National Academy of Sciences of the United States of America | | Journal Abbrev.: | Proc. Natl. Acad. Sci. U. S. A. | | Volume: | 100 | | Issue / Number: | 17 | | Start Page: | 9918 | | End Page: | 9922 | | Copyright: | Copyright © 2003 by the National Academy of Sciences | | Review Status: | not specified | | Audience: | Experts Only | | Abstract / Description: | 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. | | Comment of the Author/Creator: | Published online before print August 6, 2003, | | External Publication Status: | published | | Document Type: | Article | | Version Comment: | Automatic journal name synchronization |
| Communicated by: | Hans Lehrach | | Affiliations: | MPI für molekulare Genetik
| | External Affiliations: | GSF, Natl Res Ctr Environm & Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany.; Univ Frankfurt, Sch Med, Lab Mol Hematol, D-60590 Frankfurt, Germany.; Max Planck Inst Immunbiol, Dept Dev Biol, D-79108 Freiburg, Germany.; TU Braunschweig, Dept Cell & Mol Biol, Inst Biochem & Biotechnol, D-38106 Braunschweig, Germany.; Max Planck Inst Psychiat, Dept Mol Neurogenet, D-80804 Munich, Germany.; Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany.
| | Identifiers: | ISI:000184926000054 [ID No:1]
ISSN:0027-8424 [ID No:2] | |
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