High-Throughout Molecular Genetics

The mechanistic dissection of disease is complex and requires multi-faceted approaches in molecular genetics. For this reason, large-scale genetic projects in the IDG are divided into three areas: gene-targeting in ES cells, gene-trapping in ES cells, and ENU mutagenesis in mice. Historically, the IDG has further developed and implemented large-scale gene trapping technologies in the framework of the German Gene Trap Consortium (GGTC). Gene trap mutagenesis was the stepping stone for large scale mutagenesis programs in Europe (European Conditional Mouse Mutagenesis Consortium (EUCOMM)) and was originally used to isolate a substantial fraction of conditional mutant lines in the mouse. The ~3000 remaining genes are targeted in the IDG currently using conditional targeting technology only.

To extend the conditional EUCOMM allele resource under the EUCOMMTOOLS Program, we are currently establishing 250 Cre-driver strains expressing inducible Cre-recombinase in all unique cell-types of the body. In addition, based on the EUCOMM technology platform, high-throughput protein-tagging using fluorescent tags is used to identify protein binding partners of disease-related proteins (DiGtoP; From Disease Genes to Protein Pathways). This analysis will identify novel disease-associated proteins which might represent potential novel drug targets. Within the NGFN-funded program, EGFP-tagging of up to 400 disease genes in ES cells and mice will be established. A separate large-scale mutagenesis project includes ENU mutagenesis screens to uncover genes important for eye development and disease (collaboration with IEG).