International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Rieger S
Experimental Genetics, Neuherberg

Co-Authors: 1) Drobyshev A, 2) Schulz H, Stöger T, 3) Alessandrini F, Jakob T, Behrendt H, 4) Seliger B, 5) Graw J, 6) Ziesenis A, Schmitt-John, 7) Schachner M, 8) Willnow T, 9) Lengeling A, Hauser H, 10) Klingenspor M, 11) Chakraborty T, 1) Hrabe de Angelis M, 1*) Beckers J
Institutions: GSF-National Research Center for Environment and Health, Institutes for 1) Experimental Genetics, Neuherberg 2) Inhalation Biology, Neuherberg, 3) Division of Environmental Dermatology and Allergy, GSF/TUM, Neuherberg 4) Medizinische Klinik und Poliklinik - Johannes Gutenberg-Universität, Mainz, 5) Developmental Genetics, Neuherberg, 6) University of Bielefeld, 7) ZMN – University of Hamburg, 8) MDC - Berlin, 9) GBF Research Center Braunschweig, 10) Phillips University Marburg, 11) Justus-Liebig University Gieβen, * Coordinator of the NGFN Xpress Consortium

The NGFN Xpress is a national scientific network for RNA expression analyses of established mouse models for human disorders and basic research using DNA chip technology. We extend the systematic and standardized phenotypic analysis to the gene expression level by establishing expression profiles of organs from adult mice, embryonic tissues or from mouse cell lines. A non-redundant, near genome-wide and fully sequenced 20,000 mouse clone chip is used. Such RNA expression profiles help to identify affected molecular pathways and detect novel regulatory interactions. As examples, we present data from two collaborations. We established profiles from differentially regulated genes caused by overexpression of the oncoprotein H+er-2/neu, constitutively expressed in transformed mouse fibroblasts. Her-2/neu is a 185 kDa membrane-associated tyrosine kinase and a marker for human breast, ovarian and renal cell carcinomas. RNA expression profiles revealed significant up- and downregulation of approximately 40 and 70 genes, respectively, which appear to be involved in cell cycle regulation and cancer development. In the second example, expression profiles were generated from lungs of mice in a model study for human asthma. Ovalbumin-sensitized or non-sensitized mice were either breathing particle-free or particle-polluted air. The combinatorial analysis of differential gene expression revealed genes common to, as well as specific to the different experimental settings. The potential interpretation of this data and molecular pathways involved in immune modulation and inflammatory reactions will be discussed.

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