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Table 1 Overview of mouse models of liver fibrosis a

From: Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

Animal model Intervention Advantage Disadvantage Type of fibrosis Reference
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) [4951]
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]
  1. aCCl4, Carbon tetrachloride; NASH, Nonalcoholic steatohepatitis; TNF, Tumour necrosis factor.