Liver Diseases Models

Acute and chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, intoxications to imbalanced diets and others. Animal liver disease models are needed to mimic human liver diseases. WuXi Biology has established multiple animal liver disease models including acute liver injury; obesity related liver damage; nonalcoholic steatohepatitis (NASH); alcoholic steatohepatitis (ASH), liver fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). These models possess distinct features and etiology of human liver diseases to help evaluate the efficacy of lead compounds in relevant clinical liver diseases. They are designed to better understand the underlying mechanisms for new drugs to be used in the clinic.

In vivo animal models

Acute liver injury models

  • Alcohol induced acute liver injury in Kunming mice & non human primate (NHP)
  • CCl4 induced acute liver injury in rodents & NHP

Non Alcoholic Steatohepatitis (NASH) / HCC models

  • Fatty liver with NASH model
    • DIO + CCl4 induced NASH in mice
    • DIO + CCl4 induced NASH in NHP
    • STZ + HFD induced NASH, fibrosis, cirrhosis and HCC in mice

Complicated factor induced chronic liver injury model

  • High fat diet+alcohol+CCl4 induced liver fibrosis in monkey model

Chronic fatty liver models

  • Obesity in liver damage rodent models
    • HFD-induced fatty liver in mice and rats
    • ob/ob mice, db/db mice with fatty liver
  • Obesity and liver damage in NHP model
    • HFD-induced fatty liver in cynomolgus monkeys

Chronic liver injury models

  • Liver fibrosis/cirrhosis models
    • CCl4 induced liver fibrosis (mice, rats)
    • CCl4 induced liver cirrhosis (mice, rats)
    • Bile duct ligation (BDL) induced liver fibrosis (mice, rats)
    • Fatty liver + CCl4 induced liver fibrosis (mice, rats, NHP)
    • Fatty liver + CCl4 induced liver cirrhosis (mice, rats)
    • Alcohol induced chronic liver damage (NHP)

Endpoint Measurement

Clinical observation and physical examination

  • Body weight, behavior, food intake, water intake, defecation
  • Liver weight and spleen weight, ascite measurement, portal vein pressure

Biomarker analysis

  • Serum ALT / AST analysis
  • Gene expression and profiling (RT-PCR, microarray gene expression, miRNA)
  • Protein and metabolite profiling (WB, ELISA, mass spectrometry)
  • Hepatic hydroxyproline detection

Histology analysis

  • H&E staining in liver tissues
  • Sirius red staining and Masson Trchrome staining for collagen deposition and quantification in liver tissue
  • α-SMA IHC staining and quantification in liver tissues
  • Other related IHC staining for focused targets and markers

Representative Data

Liver damage in obese mouse models

Figure 1: Severe fatty liver was observed in high fat diet (HFD) induced DIO mice.
Figure 2: Pathology evaluation on Liver Fibrosis in Obese Mice (NASH) –HFD 20 weeks, CCl4 for 4 weeks. H&E: Hepatocyte balloon degeneration with portal area inflammatory cell infiltration. Sirius Red: Collagen deposition in portal and intra lobular area. PAS: Glycogen deposit in hepatocytes.

CCl4 induced chronic liver damage in mouse and rat models

Figure 3: CCl4 induced liver fibrosis model development in Balb/c mice, CCl4 0.5ul/g (1:5) i.p. twice a week for 8 weeks. Blood serum ALT and AST elevated significantly. Liver collagen deposition and myofibroblast proliferation have been detected.
Figure 4: Histological examination of CCl4 induced liver cirrhosis rat model. Inflammatory cell infiltration, hepatocyte degeneration, fibrosis and cirrhosis were observed.