To develop an authentic bladder cancer preclinical model in immunocompetent mice, we generated a stable organoid and xenograft model by the ex vivo transduction of adenovirus-expressing Cre recombinase into normal mouse urothelial organoid cells isolated from mice engineered with LoxP sites flanking the Trp53, Pten, and Rb1 genes. The gene discussed is RB1; the disease is urinary bladder cancer.