Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes togenes

The most important tool for obtaining insight into the function of genes is the use of mutant model organisms. Homologous recombination in embryonic s tem cells allows the systematic production of mouse mutants For any gene th at has been cloned. Gene trap strategies have been designed to interrupt ev en unknown genes which are tagged by the inserted vector and can be charact erised structurally and functionally. Complementary to such 'gene-driven' a pproaches, 'phenotype-driven' approaches are necessary to identify new gene s or gene products through a search for mutants with specific defects, unco vering the function of genetic pathways in physiological and pathological p rocesses. Mutagenesis using the alkylating agent N-ethyl-N-nitrosourea (ENU ) is a powerful approach for the production of such mouse mutants. Since EN U induces mainly point mutations in premeiotic spermatogonia, this strategy allows the production of multiple alleles of a particular gene, which is p ivotal for a Fine tuned analysis of its function.