Table 1 Overview of mouse models of liver fibrosis ^a

Bile duct ligation (BDL)

Surgical

Fast and highly reproducible

Cholestatic fibrosis

[22]

Mdr2^-/- mice

Genetic

Well-reproducible

Long latency (3 to 6 months)

Sclerosing cholangitis/biliary fibrosis

[27]

Dominant-negative TGFβRII mice

Genetic

Resembles human disease

Primary biliary cirrhosis (PBC)

[28]

IL-2Ra^-/- mice

Genetic

Resembles human disease

PBC

[29]

NOD.c3c4 mice

Genetic

Resembles human disease

Injury of the extrahepatic biliary ducts

PBC

[31]

3,5-Diethoxy-carbonyl-1,4-dihydrocollidine (DDC)

Feeding

Resembles human disease

Sclerosing cholangitis with oval cell activation

[33]

α-Naphthylisothiocyanate (ANIT)

Feeding

Fast

Cholestatic fibrosis

[34]

CCl₄ treatment

Injection, oral

Highly reproducible, fast, resembles properties of human fibrosis, good comparability due to abundant reference studies

Enhanced mortality by oral application

Toxic fibrosis

[43]

Thioacetamide (TAA) treatment

Injection, feeding

Injection, fast

Feeding, long latency

Toxic fibrosis and hepatocellular carcinoma (HCC)

[49–51]

Dimethylnitrosamine (DMN)

Injection

Fast

Mutagenic and carcinogenic

Toxic fibrosis and HCC

[58]

High-fat diet

Feeding

Fast, resembles features of insulin resistance and metabolic syndrome

Steatohepatitis and subsequent fibrosis

[70, 71]

Lieber-DeCarli diet

Feeding

Well-tolerated

Long latency, only mild injury

Alcohol-induced liver fibrosis

[73]

Methionine- and choline-deficient (MCD) diet

Feeding

Fast, strong steatohepatitis along with elevated TNF

Metabolic profile only partially reflects human NASH, no insulin resistance, body weight loss, different outcome in different mouse strains

NASH-associated fibrosis

[76, 77, 83, 84]

CD (solely choline-deficient) diet

Feeding

Resembles sequence steatosis -inflammation - fibrosis

NASH-associated fibrosis

[88]

Choline-deficient, ethionine-supplemented (CDE) diet

Feeding

Stronger NASH development compared to CD, activates hepatic progenitor cells

NASH-associated fibrosis

[90]

ob/ob mice

Genetic

Does not progress spontaneously to NASH or fibrosis

Fatty liver disease

[91]

Diethylnitrosamine (DEN) treatment

Injection

High HCC incidence, highly reproducible, well-tolerated, not associated with serious side effects

No development of fibrosis

Resembles human HCC associated with poor prognosis

[184]

DEN/CCl₄ treatment

Injection

Reflects all stages of human liver disease from chronic hepatitis leading to liver fibrosis

Resembles naturally occurring HCC progression

[194]

Liver cell–specific Nemo^-/- mice

Genetic

Spontaneous fibrosis development

Cholestatic fibrosis and HCC

[196]

Liver cell–specific Tak1^-/- mice

Genetic

Spontaneous fibrosis development

Cholestatic fibrosis and HCC

[197]