Chimeric nonhuman mammals useful as inducible spontaneous cancer models
are disclosed. The nonhuman mammals are obtained by introducing one or
more genetically modified embryonic stem (ES) cells into an early stage
embryo, and then implanting the manipulated embryo into a surrogate
mother. The ES cells contain a recombinant oncogene, and also may contain
a genetic mutation that deletes or inactivates a tumor suppressor gene.
Models of different types of cancer are produced by introducing different
combinations of genetic mutations into the ES cells that are introduced
into the early stage embryo.