International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 68 - A SYSTEMATIC, PHENOTYPE-DRIVEN MUTAGENESIS FOR GENE FUNCTION STUDIES: RECENT RESULTS OF THE MUNICH ENU-MOUSE-MUTAGENESIS SCREEN

Martin Hrabé de Angelis
GSF National Research Center

1) Soewarto D, 1) Wagner S, 3) Rathkolb B, 3) Mohr M, 3) Flaswinkel H, 1) Fuchs H,1) Marschall S, 1) Schäble K, 1) Tiedemann H, 5) Alessandrini F, 5) Jakob T, 6) Fuchs E, 6) Kolb H, 7) Kremmer E, 5) Behrendt H, 5) Ring J, 8) Zimmer A, 2) Pfeffer K, 3) Wolf E
1) GSF Research Center for Environment and Health, Neuherberg, 2) Technical University of Munich, 3) Gene Center, University of Munich, 4)Max-Delbrueck-Centre, Berlin, 5) GSF/Technical University, Munich, 6) Clinic  of Harlaching, Munich, 7)Institute of Immunology, GSF Research Center for Environment and Health, Neuherberg, 8) Polyclinic for Psychiatry, University of Bonn

With the completion of the human genome sequence and the prospect of a complete mouse sequence within the near future, a major challange is the systematic determination of gene function in mammals. The growing ENU mouse mutant resource provides a powerful entry point to gene function studies. Here, we give an update of one of the largest ENU mutagenesis programs in Europe, the Munich ENU Mouse Mutagenesis Project. Since proof-of-principle of a large-scale ENU mutagenesis program has been demonstrated during the first phase of the project by focusing on dominant traits, we put our main efforts during the last year on the recessive screen. In parallel, we continue to produce F1 animals to further isolate novel dominant alleles of known and new genes.Currently, more than 30.000 mice have been investigated for dysmorphology and blood based parameters. To date, more than 400 mutant lines have been isolated. Novel dominant or recessive phenotypes have been identified with specific abnormalities comprising congenital malformations, biochemical alterations, immunological defects and complex traits such as behaviour or predipositions to allergies. Mutants of clinical relevance for inherited diseases in human have been further analysed by backcross mapping and genome-wide microsatellite typing. Many mutant lines are under detailed phenotypic characterisation and have been proceeded for fine mapping and positional cloning.ReferencesHrabé de Angelis et al. 2000, Nat. Genet. 25, 444-447 Graw J. et al. 2001, Exp Eye Res. 73, 867-876Kiernan A. et al. 2001. PNAS 98, 3873-3878Vreugde S. et. al. 2002. Nat.Genet. 30, 257-258


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