A transgenic animal having a somatic cell in which at least one allele of
an endogenous p53 and Pten gene is functionally disrupted is provided.
The cell of the animal may be heterozygous or, more preferably,
homozygous for the gene disruptions. The animals of the invention can be
used to evaluate the efficacy of novel therapeutics and to identify novel
points of therapeutic intervention for cancer. In certain embodiments,
the transgenic animal is a transgenic mouse having functionally disrupted
endogenous p53 and Pten genes. This mouse can be used to identify agents
that inhibit the development of cancers, namely bladder cancers in humans
in vivo. Nucleic acid constructs for functionally disrupting an
endogenous p53 and Pten gene in a host cell, recombinant vectors
including the nucleic acid construct, and host cells into which the
nucleic acid construct has been introduced are also encompassed by the
invention