Institute of Molecular Animal Breeding
and Biotechnology

Prof. Dr. Eckhard Wolf, Genzentrum der LMU-München

Mouse Genetics and ENU-Mutagenesis

Animal models are essential to understand the genetics and pathogenesis of human diseases. The mouse is intensively used as a model system due to the similarity of genome organization, developmental and biochemical pathways and physiology. Mouse models can be established in a genotype- and a phenotype-driven way. A broad spectrum of transgenic (incl. pronuclear microinjection of BACs), knock-out and knock-in techniques is established in our lab and employed for our own projects and in collaboration with partners from different disciplines. In addition our lab contributes to a large enterprise aiming at the phenotype-driven generation of mouse models for human diseases: the Munich ENU Mouse Mutagenesis Screen. In this consortium we are part of the core facility and identify clinically relevant mouse models by measuring clinical-chemical and hematological parameters. With this expertise, we are also part of the recently established German Mouse Clinic (GMC), a multidisciplinary center for systematic phenotyping of mouse mutants.

Selected original papers

Hrabé de Angelis M, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Strom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung T, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25, 444-447

Rathkolb B, Decker T, Fuchs E, Soewarto D, Fella C, Heffner S, Pargent W, Wanke R, Balling R, Hrabé de Angelis M, Kolb HJ, Wolf E (2000) The clinical-chemical screen in the Munich ENU Mouse Mutagenesis Project: screening for clinically relevant phenotypes. Mamm Genome 11, 543-546

Graw J, Löster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2001) Aey2, a new mutation in the beta-B2-crystallin-encoding gene of the mouse. Invest Ophthalmol Vis Sci 42, 1574-1580

Graw J, Loster J, Soewarto D, Fuchs H, Reis A, Wolf E, Balling R, Hrabé de Angelis M (2002) V76D mutation in a conserved gamma-D-crystallin region leads to dominant cataracts in mice. Mamm Genome 13, 452-455

Dunant P, Larochelle N, Thirion C, Stucka R, Ursu D, Petrof BJ, Wolf E, Lochmüller H (2003) Expression of dystrophin driven by the 1.35 kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx mice. Mol Ther 8, 80-89

Krebs O, Schreiner CM, Scott WJ Jr, Bell SM, Robbins DJ, Goetz JA, Alt H, Hawes N, Wolf E, Favor J (2003) Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh signaling in the limb bud. Development 130, 6037-6047

Selected review articles

Rathkolb B, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (1999) Discovery and functional characterization of new genes by large scale ENU mutagenesis in mice. Arch Tierz, Dummerstorf 42, 74-85

Rathkolb B, Fuchs E, Kolb HJ, Renner-Müller I, Krebs O, Balling R, Hrabé de Angelis M, Wolf E (2000) Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes. Exp Physiol 85.6, 635-644