International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Wagner S
Institute of Experimental Genetics, GSF Research Center for Environment and Health, Germany

Co-Authors: 1) Soewarto D, 1) Wagner S, 3) Rathkolb B, 1) Fuchs H, 3) Mohr M, 3) Klempt M, 3) Howaldt M, 2) Kalaydijev S, 2) Franz T, 10) Schneider I, 1) Marschall S, 1) Boersma A, 1) Schäble K, 1) Tiedemann H, 1) Schneltzer E, 1) Steinkamp R, 5) Alessandrini F, 5) Jakob T, 9) Binder E, 6) Kremmer E, 5) Behrendt H, 5) Ring J, 7) Zimmer A, 11) Peters C, 3) Flaswinkel H, 2) Busch D, 2) Pfeffer K, 10) Klopstock T, 10) Gekeler F, 9) Ohl F, 8) Balling R, 3) Wolf E and 1) Hrabe de Angelis M
Institutions: 1) Institute of Experimental Genetics, GSF Research Center for Environment and Health, Germany, 2) Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 3) Institute of Molecular Animal Breeding, Gene Center, University of Munich, Germany, 4) Max-Delbrueck-Centre, Molekulare Genetik und Mikrosatellitenzentrum, Germany, 5) Division Environmental Dermatology and Allergology, Germany, 6) Institute of Immunology, GSF Research Center for Environment and Health, Germany, 7) Division MolecularNeurobiology, Polyclinic for Psychiatry, University of Bonn, Germany, 8) GBF German Resaerch Center for Biotechnology, 9) Max Planck Institute of Psychiatry, Munich, Germany, 10) Department of Neurology, Clinic Groβhadern, University of Munich, Germany, 11) Institute of Internal Medicine I, Medical Microbiology, University Clinic Freiburg, Germany

Mouse models have proven to play an important role in gene function studies for inherited diseases in humans. We give an update of one of the largest ENU mutagenesis programs in Europe, the Munich ENU Mouse Mutagenesis Project. After having focused on dominant traits in the first years, we put our main efforts during the last years on recessive phenotypes. In addition, we continue to produce F1 animals to further isolate novel dominant alleles of known and new genes.

Currently, more than 32.000 mice have been investigated for dysmorphology and blood based parameters. To date, more than 500 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 predispositions 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 deriving from this ENU Screen are under detailed phenotypic characterisation and have been proceeded for fine mapping and positional cloning (Kiernan et al. 2001, Graw et al. 2001). With Beethoven (Bth) (Vreugde et al. 2002) a semidominant mouse model for progressive hearing loss was found. Some new mutant lines with clinical relevance from various screens associated to the ENU project will be shown in this presentation.

A new sensitized screen with the Dll1 knockout mouse has been set up in order to identify enhancing or suppressing elements of the Delta-notch pathway. First mutants have already been isolated.

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