International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)


F1. "MouseExpress": In Silico Analysis of Expression Patterns in Mouse Mutants

Johannes Beckers1, Rainer Koenig2, Marcus Frohme3, Joerg Hoheisel3, Martin Vingron2, Werner Mewes4, and Martin Hrabé de Angelis1.
1 GSF - National Research Center for Environment and Health, Institute of Experimental Genetics, Ingolstaedter Landstr.1, 85764 Neuherberg, Germany (www.gsf.de/ieg).
2 DKFZ, Division of Theoretical Bioinformatics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (www.dkfz-heidelberg.de/tbi).
3 DKFZ, Division of Functional Genome Analysis, Im Neuenheimer Feld 506, 69120 Heidelberg, Germany (www.dkfz-heidelberg.de/funct_genome).
4 GSF - National Research Center for Environment and Health, Munich Information Center for Protein Sequences (MIPS), Klopferspitz 18, 82152 Martinsried, Germany (www.mips.biochem.mpg.de).

To systematically analyse gene function, we have initiated a project to establish expression profiles of all mutant mouse lines generated in the dominant and recessive ENU mutagenesis screens of the GSF (Germany, supported by the German Human Genome Project, www.dhgp.de). We use DNA-microarray technologies (1) to identify groups of co-expressed genes that are potentially indicative of common regulatory controls, (2) to find genetic pathways that correlate with particular phenotypes, (3) to ask which pathways (under which conditions) are co-regulated within the molecular network, and (4) to identify tissues or organs with altered gene expression, that were initially not associated with a particular mutant phenotype. In this sense, expression profiling also represents a new, molecular level of phenotypic analysis. In addition, we expect that expression profiling (in combination with preliminary mapping data) will help identify potential candidate genes for ENU mutations.

To design our DNA-chips, we have developed a software system that allows the identification of those EST clones of a given gene that have the lowest possible tendency to cross-hybridise with other expressed mouse genes. First, we are producing a chip representing approximately 500 genes, with functions during embryonic development, in cell adhesion, in the differentiation of muscle or nerve cells, in cell cycle regulation and during the development of osteoarthrosis and arthritis.

As reference we are building a database of RNA expression profiles of more than 15 organs from young adult (40 days) and adult (105 days) mice of the C3H/HeJ, C57BL/6J, and 129 SvPas strains. From the same strains we are also establishing expression profiles from 9.5 to 18.5 days of embryonic development.

To support the interpretation of our gene expression data we are developing software systems that help recognise patterns in expression profiles. Expression profiles of wildtype and mutant mice will be presented in a database linked to the phenotype and mutant database of the mouse ENU mutagenesis project of the GSF.


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