Large-scale <em>N</em>-ethyl-<em>N</em>-nitrosourea mutagenesis of mice - from phenotypes to genes

Volume 85
Issue 06 - Nov 2000
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Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes

Birgit Rathkolb, Edith Fuchs, Helmut J. Kolb, Ingrid Renner-Müller, Ottheinz Krebs, Rudi Balling, Martin Hrabé de Angelis and Eckhard Wolf (2000).
Experimental Physiology, Volume 85, Issue 06, November 2000 pp 635-643 http://journals.cambridge.org/action/displayAbstract?aid=63419

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Experimental Physiology (2000), 85 : 635-643 Cambridge University Press

Copyright © The Physiological Society 2000

doi:10.1017/S0958067000020947 (About doi)

Published online by Cambridge University Press 10 Jan 2001

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Birgit Rathkolb, Edith Fuchs, Helmut J. Kolb, Ingrid Renner-Müller, Ottheinz Krebs, Rudi Balling, Martin Hrabé de Angelis and Eckhard Wolf (2000). Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes. Experimental Physiology, 85 , pp 635-643
doi:10.1017/S0958067000020947

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Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes

Birgit Rathkolb ^a1, Edith Fuchs ^a1, Helmut J. Kolb ^a1, Ingrid Renner-Müller ^a1, Ottheinz Krebs ^a1, Rudi Balling ^a1, Martin Hrabé de Angelis ^a1 and Eckhard Wolf ^a1
^a1 Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Institute of Clinical Chemistry, Clinic Harlaching, Munich and Institutes of Mammalian Genetics and Experimental Genetics, GSF-Research Centre, Oberschleissheim, Germany

Abstract

The most important tool for obtaining insight into the function of genes is the use of mutant model organisms. Homologous recombination in embryonic stem cells allows the systematic production of mouse mutants for any gene that has been cloned. Gene trap strategies have been designed to interrupt even unknown genes which are tagged by the inserted vector and can be characterised structurally and functionally. Complementary to such 'gene-driven' approaches, 'phenotype-driven' approaches are necessary to identify new genes or gene products through a search for mutants with specific defects, uncovering the function of genetic pathways in physiological and pathological processes. Mutagenesis using the alkylating agent N-ethyl-N-nitrosourea (ENU) is a powerful approach for the production of such mouse mutants. Since ENU induces mainly point mutations in premeiotic spermatogonia, this strategy allows the production of multiple alleles of a particular gene, which is pivotal for a fine tuned analysis of its function.