Table 1.
Phenotypic comparisons. Similarities and differences among genetically engineered mouse (GEM) models of pancreatic neoplasia for chemoprevention studies
| GEM | Time of Express |
Preneo/Neoplastic Lesions | Mesenchymal | Parenchymal | Cancer Phenotype | Survival (mos) |
Caveats to Consider | Ref | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| mPanIN | mIPMN | mMCN | other | AH | ADM | Fibros | Inflam | Atrophy | Onset | Path | Inv | Met | Potential Uses | ||||
| EL-Kras | E.14 | +/− | + | + | CPN | +++ | +++ | ++ | ++ | ++ | No cancer |
No | No | 18+ | huKras; driven off EL promoter | (69) | |
| Broad screening of mult lesions | |||||||||||||||||
| Pdx1-Cre LSL-Kras |
E8.5 | +++ | ++ | +++ | 6+ | PDAC | 20% 1 yr |
Yes | 16 | Express in GI tract | (22) | ||||||
| Eval effect on PanIN lesions | |||||||||||||||||
| p48Cre LSL-Kras |
E9.5 | +++ | ++ | +++ | 8+ | PDAC | 20% 1 yr |
Yes | 16 | (22) | |||||||
| Eval effect on PanIN lesions | |||||||||||||||||
| +Mist1Kras | E10.5 + in adults |
+/− | +/− | CPN | ++ | +++ | 3 | Mixed histo |
Yes | Yes | 10.8 median |
HCC | (70) | ||||
| Broad screening of nonPanIN lesns | |||||||||||||||||
| Nest-Cre LSL-Kras |
E10.5 | ++ 1 & 2 (~100%) |
+/− | ++ | +++ | No |
No | No | 2 | Expression in brain | (71) | ||||||
| Eval effect on early PanINs | |||||||||||||||||
| EL-tTA TRE-Cre LSL-Kras |
E.16.5 P10 P60 |
3 mos 5 mos none |
+ | ++ | +++ | +++ | ++ | 12 | PDAC PDAC |
yes yes |
No No |
18+ | Kras mt G12V | (13) | |||
| Chemoprevention prior to express | |||||||||||||||||
| K5-Cox-2 | E13.5 | +/− | + | CN | ++ | +++ | +++ | near PDAC |
No | No | 6-8 | 10-week=CP;bladder abnorm | (24) | ||||
| Ability to inhibit Cox-2 | |||||||||||||||||
| Pdx1-CreERT LSL-Kras |
E.10.5 P14,21, 24,27,56 |
2-4 mos 1-2 lower in P56 |
++ | +++ | ++ | +++ | study terminated at 4 mos. | addition of R26NIC increase number & severity of mPanINs |
(11) | ||||||||
| 6 | PDAC | NR | NR | term at 6m |
Chemoprevention prior to express | ||||||||||||
| EL-CreERT LSL-Kras |
P42 | 1-30% 2-18% 3-3% |
++ | ++ | ++ | No cancer |
No | No | term at 16 mos. |
addition of R26NIC increase number & severity of mPanINs |
(11, 14) | ||||||
| Chemoprevention prior to express | |||||||||||||||||
| Mist1CreERT LSL-Kras |
P42 | 2 mos (like EL target) |
++ | No cancer | No | No | term at 12 mos. |
Targeting of liver cells | (14) | ||||||||
| Chemoprevention prior to express | |||||||||||||||||
| EL-CreERT cLGL-Kras |
E16+ | 0-2 = 1,2 2-6 = 1-3 6-9 =inc3 |
++ | +++ | ++ | ++ | 4+ | CPC PDAC |
Yes | Yes | Cre expression without tamoxifen | (15) | |||||
| Chemoprevention prior to express | |||||||||||||||||
| pCPA1CreERT LSL-Kras |
P14,21, 24,27,56 |
1 – 10% | NR | NR | NR | NR | No cancer |
No | No | term at 3 mos. |
addition of cerulein increase number & severity of mPanINs |
(12) | |||||
| RipCreERT LSL-Kras |
P14,21, 24,27,56 |
none | No cancer |
No | No | up to 8 mos |
addition of cerulein leads to development of mPanINs |
(12) | |||||||||
Abbreviations: ADM, acinar-ductal metaplasia; AH, acinar hyperplasia; Cox-2, cyclooxygenase-2; CN, cystic neoplasms; CP, chronic pancreatitis; CPC, cystic papillary carcinoma; CPN, cystic papillary neoplasms; EL-Kras, elastase-driven mutant Kras; EL-tTA, EL tetracycline transactivator; Fibros, fibrosis; histo, histology; Inflam, inflammation; Inv, invasive; LSL-Kras, Lox-Stop-Lox-responsive mutant Kras; Met, metastatic; mIPMN, mouse intraductal papillary mucinous neoplasia; Mist1Cre, knock-in of Cre upstream of the Mist1 coding region; Mist1Kras, knock-in of mutant Kras upstream of the Mist 1 coding region; mMCN, mouse mucinous cystic neoplasia; mPanIN, mouse pancreatic intraepithelial neoplasia; NR, not reported; p48Cre, knock-in of Cre upstream of the p48/Ptfa coding region; pCPA1CreERT, procarboxypeptidase A1-responsive CreERT; PDAC, pancreatic ductal adenocarcinoma; RipCreERT, rat insulin promoter-responsive CreERT; TRE-Cre, tetracycline-responsive Cre.