Modifier Validation

Coordinator:		Dr. Markus Morkel
Institution:		Max-Planck-Institut für molekulare Genetik
Homepage:		www.molgen.mpg.de

The role of this subproject in the consortium is the generation of mouse models for validation of candidate modifier genes identified in the collaborating subprojects. We will consider genes, which are consistently found to be up-regulated or de-novo methylated during tumor initiation or progression in human colon tumors and in APC-min mice carrying a PWD derived modifier, and can be correlated with changes in tumor pathology parameters. Such correlation of molecular phenotypes with pathological phenotypes is a good indication of functional relationships, which need to be confirmed in the animal model.
To this end, we use advanced tumor models to integrate modifier genes into the mouse genome in a controlled manner. Mice carrying such a transgene can be crossed to APCmin mice, and the tumor phenotype can be assessed in the compund mutants. Approaches for modifier validation include modifier overexpression, modifier knockdown, inducible expression of modifier gene variants and other genetic models. Functional validation of modifier genes is a prerequisite to clinical applications.