Table 3.
GEM models of bladder cancer
Allele name | Method for targeting to bladderb | Description | Phenotype | Ref. |
---|---|---|---|---|
Transgenic models | ||||
UPII-SV40Ta | Uroplakin II Promoter | Expression of SV40 large T antigen | CIS | 126, 127 |
UPII-SV40T high | CIS with progression to invasion, in some cases metastasis | 126 | ||
CK19-SV40T | Cytokeratin 19 | CIS with progression to invasion, in some cases metastasis | 129 | |
UPII-Ha-RasQ61L | Uroplakin II | Expression of mutant (active) H-Ras | Papillary non-invasive cancer | 131 |
UPII-EGFR | Expression of EGFR | Hyperplasia | 132 | |
UPII-SV40T low; EGFR | Expression of SV40 large T combined with EGFR | High-grade non-invasive cancer | 132 | |
UPII-p53DN | Expression of mutant (active) p53 | Hyperplasia | 135 | |
UPII-Ha-rasQ61L; p53DN | Mutant (active) H-Ras combined with mutant (active) allele of p53 | Hyperplasia with localized dysplasia | 135 | |
UPII-Ha-rasQ61L; p53-null | Mutant H-Ras combined with a germline null allele of p53 | Papillary non-invasive cancer | 135 | |
Models using Cre Drivers expressed in the urothelium | ||||
β-cateninexon3/exon3 | UroII-Cre allele | Mutant (active) allele of β-catenin | Hyperplasia | 136 |
β-cateninexon3/exon3; Ptenflox/flox | Mutant (active) allele of β-catenin combined with loss of function of Pten | Papillary non-invasive cancer | 136 | |
β-cateninexon3/exon3; K-rasG12D | Mutant (active) allele of β-catenin combined with mutant (active) Kras | Papillary non-invasive cancer | 137 | |
β-cateninexon3/exon3; H-rasQ61L | Mutant (active) allele of β-catenin combined with mutant (active) Ha-ras | Papillary non-invasive cancer | 137 | |
β-cateninexon3/exon3; p21−/− | Mutant (active) allele of β-catenin combined with germline null allele of p21 | Papillary non-invasive cancer | 137 | |
Fgfr3+/K644E; Ptenflox /flox | Mutant (active) allele of Fgfr3 combined with loss of function of Pten | Hyperplasia with localized dysplasia | 140 | |
UPII-Ha-rasQ61L; CDKN2A null | Mutant H-Ras combined with a germline null allele of INK4a/Arf | Hyperplasia | 134 | |
Ncstnflox/flox | UPII-Cre-GFP | Bladder-restricted deletion of Nicastrin, which abrogates Notch function | Hyperplasia and CIS | 139 |
Models using Cre Drivers that are not specific for bladder | ||||
β-cateninexon3/+ | Msx2rtTA;tetO-Cre | Mutant (active) allele of β-catenin | Papillary non-invasive cancer | 58 |
Ptenflox /flox | Fabp-Cre | Conditional loss of function Pten | Papillary non-invasive cancer | 150 |
Lkb1flox/flox; Ptenflox/flox | AhCreER | Conditional loss of function of Lkb and Pten | Papillary non-invasive cancer | 141 |
Ncstnflox/flox | Rosa26rtTA;tet O-Cre | Systemic deletion of Nicastrin, which abrogates Notch function | Muscle-invasive bladder cancer | 139 |
Models using delivery of Adeno-Cre to the bladder | ||||
p53flox/flox; Ptenflox/flox | AdenoCre delivery (via surgery) | Conditional loss of function of p53 and Pten | Muscle-invasive bladder cancer with frequent metastasis | 112 |
p53flox/flox; K-rasG12D | AdenoCre delivery (via instillation) | Mutant (active) allele of β-catenin combined with mutant (active) Kras | Hyperplasia | 143 |
Rbflox/flox; p130flox/flox p107−/− | AdenoCre delivery (via surgery) | Loss of function of all retinoblastoma genes | Papillary non-invasive cancer | 159 |