Metabolic in vivo Models

liver disease models, nonalcoholic steatohepatitis, cirrhosis, HCC, NAFLD, dyslipidemia

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.

Diabetes & Diabetic Complications
Obesity
Dyslipidemia models
Liver injury models
Endpoint Measurements

Diabetes & Diabetic Complications

Spontaneous Diabetes db/db Mice, ZDF Rats
High-fat Diet Induced Diabetes Multiple species
Type 1 Diabetes ModelStreptozotocin (STZ) induction
Type 2 Diabetes Model db/db mouse
Type 2 Diabetes Model ob/ob mouse
Type 2 Diabetes Model Zucker diabetic fatty (ZDF) rat
Type 2 Diabetes Model High-fat diet / STZ induction
Diabetic Nephropathy ModelStreptozotocin (STZ) induction
Diabetic Nephropathy Model db/db mouse
Diabetic neuropathic painChronic Neuropathic Pain
Diabetic ComplicationsRetinopathy (retina vascular leakage)
Diabetic ComplicationsWound Healing

Obesity

Spontaneous Obesity(ob/ob Mice, Aged CD-1 Mice, fa/fa Rats)
Foodintake ScreeningMutiple species
Diet Induced Obesity (DIO) ModelHigh-fat diet (HFD) induction
Diet Induced Obesity (DIO) Model hGLP1r humanized mouse, high-fat diet (HFD) induction

Dyslipidemia models

Hyperlipidemia ModelHigh cholesterol diet (HCD) induction
Hyperlipidemia ModelHigh fat diet/cholesterol/fructose diet (HFD/WD) induction

Liver injury models

Acute liver injury modelsAlcohol induced acute liver injury in Kunming mice & NHP
Acute liver injury modelsCCl4 induced acute liver injury in rodents & NHP
Chronic liver injury modelsCCl4 induced liver fibrosis (mice, rats)
Chronic liver injury modelsCCl4 induced liver cirrhosis (mice, rats)
Fibrosis ModelBile duct ligation (BDL) induced liver fibrosis (mice, rats)
Fibrosis ModelFatty liver + CCl4 induced liver fibrosis (mice, rats, NHP)
Fibrosis ModelFatty liver + CCl4 induced liver cirrhosis (mice, rats)
Non-Alcoholic Fatty Liver Disease (NAFLD Model) High-fat diet (HFD) induction
Non-Alcoholic Steatohepatitis (NASH) ModelHigh-fat diet (HFD) and carbon tetrachloride (CCL4) induction
Non-Alcoholic Steatohepatitis (NASH) ModelCholine-deficient and high-fat diet (CDHFD) induction
NASH-like ModelMethionine and choline deficient (MCD) diet induction
NASH-like ModelStreptozotocin (STZ) and high-fat diet (HFD) induction
Complicated factor induced chronic liver injury modelHigh fat diet+alcohol+CCl4 induced liver fibrosis

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

DIO mouse model, fatty liver, NAFLD, HFD high-fat diet
Figure 1: Severe fatty liver was observed in high fat diet (HFD) induced DIO mice.
NASH, liver fibrosis, glycogen deposit, CCl4 and HFD, pathology evaluation
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

CCl4 induced chronic liver damage in mouse and rat models
AST and ALT levels in rodent models, induced by carbon tetrachloride, CCl4
carbon tetrachloride induced liver fibrosis model in BALB/c mice, collagen deposits
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.
Histology, histological evaluation of CCl4 induced liver cirrhosis in rat model, cell infiltration, hepatocytes
Figure 4: Histological examination of CCl4 induced liver cirrhosis rat model. Inflammatory cell infiltration, hepatocyte degeneration, fibrosis and cirrhosis were observed.
Cardiovascular & Metabolic Diseases

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