Metabolic in vivo 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.
Diabetes & Diabetic Complications
| Spontaneous Diabetes | db/db Mice, ZDF Rats |
| High-fat Diet Induced Diabetes | Multiple species |
| Type 1 Diabetes Model | Streptozotocin (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 Model | Streptozotocin (STZ) induction |
| Diabetic Nephropathy Model | db/db mouse |
| Diabetic neuropathic pain | Chronic Neuropathic Pain |
| Diabetic Complications | Retinopathy (retina vascular leakage) |
| Diabetic Complications | Wound Healing |
Obesity
| Spontaneous Obesity | (ob/ob Mice, Aged CD-1 Mice, fa/fa Rats) |
| Foodintake Screening | Mutiple species |
| Diet Induced Obesity (DIO) Model | High-fat diet (HFD) induction |
| Diet Induced Obesity (DIO) Model | hGLP1r humanized mouse, high-fat diet (HFD) induction |
Dyslipidemia models
| Hyperlipidemia Model | High cholesterol diet (HCD) induction |
| Hyperlipidemia Model | High fat diet/cholesterol/fructose diet (HFD/WD) induction |
Liver injury models
| Acute liver injury models | Alcohol induced acute liver injury in Kunming mice & NHP |
| Acute liver injury models | CCl4 induced acute liver injury in rodents & NHP |
| Chronic liver injury models | CCl4 induced liver fibrosis (mice, rats) |
| Chronic liver injury models | CCl4 induced liver cirrhosis (mice, rats) |
| Fibrosis Model | Bile duct ligation (BDL) induced liver fibrosis (mice, rats) |
| Fibrosis Model | Fatty liver + CCl4 induced liver fibrosis (mice, rats, NHP) |
| Fibrosis Model | Fatty liver + CCl4 induced liver cirrhosis (mice, rats) |
| Non-Alcoholic Fatty Liver Disease (NAFLD Model) | High-fat diet (HFD) induction |
| Non-Alcoholic Steatohepatitis (NASH) Model | High-fat diet (HFD) and carbon tetrachloride (CCL4) induction |
| Non-Alcoholic Steatohepatitis (NASH) Model | Choline-deficient and high-fat diet (CDHFD) induction |
| NASH-like Model | Methionine and choline deficient (MCD) diet induction |
| NASH-like Model | Streptozotocin (STZ) and high-fat diet (HFD) induction |
| Complicated factor induced chronic liver injury model | High 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
NAFLD: READ OUR NASH CASE STUDY
CLINICAL RELEVANCE OF NASH ANIMAL MODELS:
AN ANIMAL CASE FOR RESMETIROM AND OBETICHOLIC ACID
NASH Case Study Data
Anti-fibrotic activity of OBETICHOLIC ACID (OCA) in HFD+CCL4 model
The fibrosis in portal tract and perilobular regions are highlighted by green and blue arrows, respectively, in the NASH model (left). The OCA treatment improves the fibrosis in these two regions (right).
SHG/TPE digital histopathology and quantification of fibrotic septa in healthy control, HFD and CCL4 induction, and NASH (HFD+CCL4) model with and without OCA treatment. A. Representative fields of SHG/TPE microscopies, with fibrotic septa labeled in pink. B. Total fibrosis. C. Fibrotic septa.
Compilation of hepatic fibrosis in rodent models
A). HFD+CCL4 and MCD models. B). Other rodent models with hepatic fibrosis, top left: CDHFD model.
Quantitative histopathological analysis of fibrosis associated with steatosis in CCL4 induction (only fibrosis) and
HFD+CCL4 model with vehicle and OCA treatment.
