Recently, we identified the gene responsible for X- linked Opitz syndrome. The gene product of the so-called MID1gene is a member of the RING finger protein family, sharing 6 different protein domains with a subset of members of this family. The best known of these proteins is the PML protein which, after fusion with the retinoic acid receptor, is involved in the pathogenesis of promyelocytic leucemia.
By employing GFP fusion proteins, we showed that the MID1 protein is associated to microtubules. Mutant proteins, as found in OS patients, no longer bind to microtubules but form cytoplasmic clots instead.

These findings are attractive models to use in explaining the molecular pathogenesis of OS. A loss of function of MID1 at its physiological localization at the microtubules obviously leads to the development of a highly specific and complex human phenotype. An important key to understanding the mechanisms behind the responsible events during embryogenesis is the physiological function of the microtubules-associated MID1 protein. Thus, the elucidation of the cellular pathways involving the MID1 protein is one of our main points of focus.
The project is being carried out in close collaboration with a group in Innsbruck / Austria performing two- hybrid screens as well as various in vitro assays characterizing MID1 interacting proteins identified. We are mainly concentrating on the cellbiological part of the work, using diverse eucaryotic expression systems for immunofluorescense and immunoprecipitation. In addition, we are in the process of isolating the MID1 functional complex via immunoprecipitation, affinity- chromatography, 2D-PAGE and mass spectrometry.