High-Throughput 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 gene trapping and gene targeting mutagenesis programs in Europe (European Conditional Mouse Mutagenesis Consortium (EUCOMM)).

EUCOMM was a founding member of the International Knock-out Mouse Consortium (IKMC) which together generated about 18.500 mostly conditional mutant ES cells. The remaining genes of the mouse genome are currently mutated by CRISPR/Cas9 genome editing technologies (see also Genetic Tools Development). Based on this resource already more than 6.000 mutant mice have been established and phenotyped - mostly be the International Mouse Phenotyping consortium (IMPC). Thus, by this international enterprise already for about one third of all mammalian genes mutant mice have been produced. By now more than 1.500 publications acknowledge the use of EUCOMM material, a number which will increase during the next years.

To extend the conditional EUCOMM allele resource under the EUCOMMTOOLS Program, we established 230 Cre-driver strains expressing inducible Cre-recombinase in all unique cell-types of the body. 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.