Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes

Table 1 Hepatitis B virus-related transgenic mice

Transgene	Promoter	Expression	Pathology	Ref.
PreS/S/X	Endogenous	Surface proteins	Until 6 mo: no obvious pathology	[28]
PreS/S/X (two TGs)	Endogenous and mouse metallothionein I	Surface proteins	Not determined	[29]
PreS/S/X	Mouse metallothionein I and Albumin	Surface proteins	Ground glass	[22,30-32,34]
			7-9 mo: adenoma
			12 mo: HCC
			18 mo: HCC (100%)
Genome (2X)	Endogenous	Surface proteins	Not determined	[241]
PreS/S (Knock-in)	Mouse p21	Surface proteins	15-24 mo: HCC [53% (♂KI/+), 72% (♂KI/KI), 0% (♀KI/+ and KI/KI)]	[37]
PreS/S	Endogenous	Surface proteins	HCC	[33,40]
X	Human α-1-antitrypsin	HBx protein	Focal necrosis, hyperplasia nodule (Authors claimed that X is not tumorigenic)	[42]
X	Endogenous	HBx protein	4 mo: altered hepatocyte in multifocal area	[43,44]
			10 mo: tumor nodule
			16 mo: tumor (80%)
			24 mo: HCC (84%)
X	Endogenous	HBx protein	6 mo: neoplastic nodules (66.6%)	[41]
			15-18 mo: small neoplastic nodule (100%) and HCC (75%)
X (Knock-in)	Mouse p21	HBx protein	15-24 mo: HCC [60%-64% (♂KI/+ and KI/KI), 43%-46% (♀KI/+ and KI/KI)]	[37]
X	Mouse albumin	HBx protein	12 mo: dysplasia nodule (100%)	[45-47]
			16 mo: HCC (80%)
			20 mo: HCC (90%-100%)
Precore/core	Mouse metallothionein I	Precore protein	Not determined	[56]
Precore/core	Endogenous	Core protein	12 mo: no hepatitis or HCC	[13,57]
Precore/core (two TGs)	Endogenous	Precore and core proteins	Not determined	[58]
Genome (2X)	Endogenous	Replicative intermediates	10 mo: no obvious pathology	[60]
Genome (1.2X)	Endogenous	Replicative virus	12 mo: no hepatitis or HCC	[59,61]
			24 mo: no obvious pathology
Genome (1.3X)	Endogenous	Replicative intermediates	Until 12 mo: no obvious pathology	[62]

PreS/S: Coding region of hepatitis B virus (HBV) large, middle and small surface proteins; X: Coding region of HBV X protein; Precore/core: Coding region of HBV pre-core/core proteins; KI: Knock-in allele; TG: Transgenic mice; Genome (2X): Indicates 2 copies of the complete 3.2-kilobase HBV genome.