Table 2.

Mouse models of bladder cancer

Type of model	Description	Advantages	Disadvantages
Non-autochthonous models
Orthotopic engraftment models	Primary urothelial or bladder cancer cells implanted into the bladder wall of recipient hosts such that tumors arise in the bladder	Ease of functional analyses of candidate genes Preclinical models for either intravesical or systemic therapy	Engrafted tumors do not develop de novo Tumors arise in immunodeficient mice and therefore may not inform on the role of the immune system
Renal grafting models	Urothelial or bladder cells are combined with embryonic bladder mesenchyme and grown under the kidney capsule of recipient hosts	Ease of functional analyses of candidate genes Investigate epithelial-mesenchymal tissue interactions Preclinical models for systemic therapy
Patient derived Xenografts (PDX)	Engraftment of patient tumors into recipient mice	Potential to model individual patient tumors Potential to model specific bladder cancer subtypes Preclinical analysis of agents for specific patient tumors	Tumors arise in immunodeficient mice Take-rate may differ depending on the tumor phenotype or sub-type No definitive evidence that responses in the PDX models will translate to patients
Autochthonous Carcinogen-based models
Carcinogen-based	Treatment of mice with carcinogens in the drinking water, the most common is BBN	Mimic environmental exposures associated with human bladder cancer Not limited to mice; work in various species Can be combined with GEM models to exacerbate their bladder cancer phenotypes	Heterogeneity of cancer phenotypes makes it difficult to use for molecular investigations or preclinical studies Metastases are rare
Autochthonous GEM models
Transgenic models	Expression of oncogenes in the urothelium (such as expression of SV40 Large T antigen)	Original in vivo models of bladder cancer	Limited options to express genes specifically in the bladder Phenotypes of single alleles, and even most compound alleles, are relatively modest Few models develop invasive bladder cancer Rare occurrence of metastases
Germline models	Loss of function of tumor suppressor genes in the germline (such as p53 null mice)	Phenotypes can be enhanced using BBN
Conditional alleles	Conditional or inducible gene recombination of oncogenes or tumor suppressor genes in the urothelium (such as deletion of Pten and p53)	Range of bladder tumor phenotypes