| abstract |
Methods, transformation constructs, and transgenic animals for identifying anti-tumor agents and anti-tumor drug targets are described. The transformation constructs are used to generate transgenic animals that have altered expression of an oncogene or tumor suppressor gene in a target tissu e that is dispensable for viability and reproduction. In some embodiments, the altered expression results in abnormal proliferation of the target tissue an d normal proliferation in all other tissues. Anti-tumor drug targets can be identified by generating progeny of the transgenic animals that have mutatio ns in various genes. Gene mutations that result in a specific reduction or killing of the target tissue are identified as possible anti-tumor drug targets and are further evaluated. Anti-tumor agents are identified that mim ic the effect of the gene mutations that result in specific reduction of the target tissue. Alternatively, anti-tumor agents can be identified by administering various compounds directly to the transgenic animals, or their progeny, and selecting as putative therapeutic agents, compounds that result in target-tissue specific antiproliferation. |