Table 1.
GEMMs of extrahepatic tumorigenesis
| Name | Tumor location | Phenotype | Tumor latency | Reference | |
|---|---|---|---|---|---|
| KT‐K19 CreERT model: LSL‐Kras G12D; Tgfbr2 flox/flox; Krt19 CreERT | Kras G12D activation; Tgfbr2 loss; Cdh1 loss | EHBDs, PBGs | Biliary hyperplasia | 3 months∼ | Nakagawa et al. 85 |
| Under the control of Krt19 promoter | |||||
| KTC‐K19 CreERT model: LSL‐Kras G12D; Tgfbr2 flox/flox; Cdh1flox/flox; Krt19 CreERT | Kras G12D activation; Tgfbr2 loss; Cdh1 loss | EHBDs, PBGs | Invasive carcinoma (moderately/poorly differentiated adenocarcinoma) | 4 weeks∼ | Nakagawa et al. 85 |
| Under the control of Krt19 promoter | |||||
| S+ KPP model: Sox9‐CreERT2; LSL‐Kras G12D; PTEN flox/flox | ‐ | EHBDs, PBGs, GB neck, pancreas head | Biliary adenoma (IPNB with low/mediate dysplasia) In this model, tumor lesions are more malignant outside of EHBD | 3 months ∼ (after TM) | Lin et al. 86 |
| Under the control of Sox9 promoter | |||||
| iFGF10 model: Rosa26‐rtTA; Tet‐Fgf10‐ires‐tdTomato | Fgf10 overexpression | EHBDs, PBGs, large IHBDs, GB neck | BilIN, IPNB, IPNB with invasive carcinoma (with Kras G12D, p53 R172H, and/or p16 flox/flox mice) | 4 weeks ∼ (Dox continuous administration) | Tomita et al. 77 |
| Under the control of Rosa26 promoter | |||||
| Pdx1‐FGF10 model: LSL‐rtTA; Pdx1‐Cre; Tet‐Fgf10‐ires‐tdTomato | Fgf10 overexpression | EHBDs, PBGs, GB neck, pancreas | IPNB, IPNB with invasive carcinoma (with Kras G12D, p53 R172H, and/or p16 flox/flox mice) | 4 weeks ∼ (Dox continuous administration) | Tomita et al. 77 |
| Under the control of Pdx1 promoter | |||||
| Krt19‐FGF10 model: LSL‐rtTA; Krt19‐iCre; Tet‐Fgf10‐ires‐tdTomato | Fgf10 overexpression | EHBDs, PBGs, large IHBDs, GB neck | IPNB, IPNB with invasive carcinoma (with Kras G12D, p53 R172H, and/or p16 flox/flox mice) | 4 weeks ∼ (Dox continuous administration) | Tomita et al. 77 |
| Under the control of Krt19 promoter | |||||
| Sox9‐FGF10 model: LSL‐rtTA; Sox9‐CreERT2; Tet‐Fgf10‐ires‐tdTomato | Fgf10 overexpression | EXHBDS, PBGs, large IHBDs, GB neck | IPNB, IPNB with invasive carcinoma (with Kras G12D, p53 R172H, and/or p16 flox/flox mice) | 4 weeks ∼ (Dox continuous administration after TM) | Tomita et al. 77 |
| Under the control of Sox9 promoter |
Note: Alb‐FGF10 model (LSL‐rtTA; Alb‐Cre; Tet‐Fgf10‐ires‐tdTomato) develops BilIN, IPNB, and cholangiocarcinoma only in small and large IHBDs (Tomita et al. 77 ). Hepatocyte‐FGF10 model (LSL‐rtTA; Tet‐Fgf10‐ires‐tdTomato with AAV‐Ttr‐Cre injection) develops BilIN and IPNB only in small and large IHBDs (Tomita et al. 77 ).
Abbreviations: BilIN, biliary intraepithelial neoplasia; Dox, doxycyclin; EHBD, extrahepatic bile duct; GB, gallbladder; GEMMs, genetically engineered mouse models; IHBD, intrahepatic bile duct; IPNB, intraductal papillary neoplasms of the bile duct; PBG, peribiliary gland; TM, tamoxifen.