The cloning of a disease-associated gene such as the NF2 gene provides immediate hope for the development of effective treatments. However, the path toward that goal remains long, despite the knowledge of the underlying genetic defect. An understanding of the normal function of the NF2-encoded protein and cell behavioral and molecular consequences of its loss is critical to further progress. The generation of an animal model can provide several invaluable resources toward this goal. Importantly, the manipulability of an animal model allows us to identify the normal function that the Nf2-tumor suppressor evolved to perform by generating animals that completely lack Nf2 function, a situation that rarely, if ever, arises in humans. We have generated a strain of mice that carries a mutation in the mouse Nf2 gene, and therefore genetically mimics human NF2 patients. The study of these cancer-prone mice suggests that the NF2 tumor suppressor and the family of proteins to which it belongs may play a much more important role in human cancer development and progression than expected. Importantly, we have also identified multiple roles for the NF2 protein in mouse development, allowing us to study the consequences of Nf2-deficiency in the whole organism in the context of the roles it evolved to perform. The goal of this proposal is to study the function of the Nf2 tumor suppressor in the cellular contexts that we have found to be affected by its loss in the mouse. |
