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

Published online by Cambridge University Press:  10 January 2001

Birgit Rathkolb
Affiliation:
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
Edith Fuchs
Affiliation:
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
Helmut J. Kolb
Affiliation:
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
Ingrid Renner-Müller
Affiliation:
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
Ottheinz Krebs
Affiliation:
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
Rudi Balling
Affiliation:
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
Martin Hrabé de Angelis
Affiliation:
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
Eckhard Wolf
Affiliation:
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
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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.

Type
Research Article
Information
Experimental Physiology , Volume 85 , Issue 6 , November 2000 , pp. 635 - 643
Copyright
© The Physiological Society 2000

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