Cre/loxP-based Mouse Model for Hepatocellular Carcinoma

Cre/loxP-based cancer mouse models allow tumors to form within their physiologic environment in a temporally and spatially controlled manner. Albumin-floxstop-Tag (AST) mice contain a loxP-flanked stop cassette followed by the oncogenic SV40 large T antigen (Tag) under the control of the albumin-promoter/enhancer sequence to limit the expression of Tag to hepatocytes (39 (link), 40 (link)). Tag initiates tumor formation by inhibiting tumor suppressors, including p53 and Rb family members, and is also a potent antigen target for CD8 T cells (41 (link)). Cre recombinase excises the stop cassette, initiating Tag expression. Cre recombination can be mediated, and tumors were initiated as follows: ASTxAlb:Cre AST mice are crossed to Alb:Cre [Alb:Cre (B6.Cg-Tg(Alb-cre)21Mgn/J)] mice (Jackson Laboratories), which constitutively express Cre recombinase in hepatocytes. In ASTxAlb:Cre mice, Cre recombinase leads to the excision of the stop cassette neonatally and results in SV40 Tag oncogene expression and subsequent tumor initiation in hepatocytes after birth.

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Tee S.S., Kim N., Cullen Q., Eskandari R., Mamakhanyan A., Srouji R.M., Chirayil R., Jeong S., Shakiba M., Kastenhuber E.R., Chen S., Sigel C., Lowe S.W., Jarnagin W.R., Thompson C.B., Schietinger A, & Keshari K.R. (2022). Ketohexokinase-mediated fructose metabolism is lost in hepatocellular carcinoma and can be leveraged for metabolic imaging. Science Advances, 8(14), eabm7985.

Publication 2022

Alb:Cre (B6.Cg-Tg(Alb-cre)21Mgn/J)]

Albumin Antigen Birth Cancer Cd8 t cells Cre recombinase Family members Hepatocytes Large t antigen Mice Oncogene Physiologic Recombination Sv40 T antigen Tumor Tumor suppressors

Corresponding Organization : Cornell University

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Variable analysis

independent variables

Presence of Cre recombinase

dependent variables

Excision of the stop cassette
Expression of the SV40 Tag oncogene
Tumor initiation in hepatocytes

control variables

Albumin-floxstop-Tag (AST) genotype
Alb:Cre (B6.Cg-Tg(Alb-cre)21Mgn/J) genotype

controls

Positive control: ASTxAlb:Cre AST mice, where Cre recombinase leads to the excision of the stop cassette neonatally and results in SV40 Tag oncogene expression and subsequent tumor initiation in hepatocytes after birth.
Negative control: Not explicitly mentioned.

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