Table 3.
HCC animal models with CTNNB1 manipulation.
| Animal | Method * | Expression ** |
CTNNB1 Status *** |
Results | Ref. |
|---|---|---|---|---|---|
| Mice |
Alb promoter |
+ | Wildtype | Transgenic mice develop hepatomegaly but no tumors | [71] |
|
Alb promoter |
+ | Ser45 mutated | Transgenic mice develop hepatomegaly (only in younger mice) but no tumors; Increased HCC (DEN induction) | [72] | |
| Fabp: Cre | + | Exon 3 deleted |
Transgenic mice develop hepatomegaly but no tumors | [73] | |
|
CaBP9K promoter |
+ | N131 deleted | Transgenic mice develop hepatomegaly but no tumors | [74] | |
| Cited1: CreER | + | Exon 3 deleted |
Transgenic mice develop HCCs, hepatoblastomas, and lung metastases | [79] | |
| AdCMV-Cre | + | Exon 3 deleted (and H-RAS) | Double transgenic mice develop HCC, but no HCC develops with expression of mutated CTNNB1 alone | [78] | |
| SB-HDT | + | S45 or S33 mutated (and MET) | Mice expressing MET and either form of mutated CTNNB1, but not mutated CTNNB1 alone, develop HCC | [75] | |
| SB-HDT | + | N90 deleted (and activated YAP) | Mice expressing activated YAP and mutated CTNNB1, but not mutated CTNNB1 alone, develop HCC | [76] | |
| SB-HDT | + | S45 or S33 mutated (and K-RAS) | Mice expressing K-RAS and either form of mutated CTNNB1, but not mutated CTNNB1 alone, develop HCC | [77] | |
| siRNA | − | S45 mutated (HDT induction) |
Decreased HCC (K-RAS plus S45-mutated CTNNB1 HDT induction) | [77] | |
| Alb:Cre | − | Wildtype (endogenous) |
Increased HCC (DEN induction) | [82] | |
| Alb:Cre | − | Wildtype (endogenous) |
Increased HCC (MET and N90-deleted CTNNB1 induction) | [83] | |
| Zebrafish | fabp10a promoter | + | S33A, S37A, T41A, and S45A mutated | Transgenic zebrafish develop HCC as adults (78% by 6 months) | [81] |
| fabp: CreERT2 | + | Transgenic zebrafish develop HCC as adults (13% by 6 months) | [80] |
*: Method indicates promoter or method used to express or target CTNNB1. **: +, CTNNB1 overexpression or expression of activated form of CTNNB1; -, CTNNB1 knockout or knockdown. ***: For gain-of-function (+) studies, CTNNB1 status indicates the wildtype or activated form of the gene that is expressed in each study. Other genes targeted in the model are shown in parentheses. For loss-of-function (−) studies, the form of the targeted CTNNB1 allele is shown, with its origin indicated in parentheses. Abbreviations: Alb, albumin; Fabp, fatty acid-binding protein; Fabp: Cre, Fabp promoter driving expression of Cre recombinase; CaBP9K, calbindin-D9K; Cited1: CreER, Cited1 driving expression of tamoxifen-inducible Cre (CreER); AdCMV-Cre, recombinant adenovirus with cytomegalovirus promoter driving Cre recombinase; SB-HDT, sleeping beauty transposase-mediated hydrodynamic transfection; Alb: Cre, albumin promoter driving Cre recombinase; and DEN, diethylnitrosamine.