Introduction to NASH Mouse Models for Research
Nonalcoholic steatohepatitis (NASH) is a serious and progressive form of nonalcoholic fatty liver disease (NAFLD). NAFLD broadly represents multiple disorders and is marked by excessive fat accumulation in the liver, while NASH is characterized by several pathological changes including inflammation and cell damage in addition to fat accumulation in the liver. As fat accumulates in hepatocytes, a downstream immune response is triggered, leading to inflammation in liver tissue that can potentially lead to scarring and fibrosis.
While the mechanism of NASH progression is not fully understood, the co-existence of obesity, insulin resistance, and metabolic syndrome increases the risk of developing NASH. NASH mouse models used in preclinical experiments are either diet-induced, genetically engineered, a combination of the two or pharmacological models.
While it is challenging to mimic all the pathological features of human disease, to understand the mechanisms underlying NASH induction and progression, and to develop innovative therapies we established several NASH mouse models representing different stages of disease pathogenesis.
Our selection of NASH mouse models
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Carbon Tetrachloride (CCl4)-induced Model
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A well-established and widely accepted experimental mouse model to study liver fibrosis and cirrhosis is via Carbon tetrachloride (CCl4) injection. In many aspects, CCl4-induced hepatic fibrosis and cirrhosis in murine models mirrors the pattern of toxic damage seen with human disease, such as presence of stellate cell activation, macrophage infiltration, and alterations in matrix components including collagen-1, matrix metalloproteinases (MMPs) and their inhibitors. CCl4 injection elicits a reproducible and predictable fibrotic and cirrhotic response in the liver, making it a valuable preclinical resource for pharmacological and pathophysiological studies.
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HFMCD induced NASH Model
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This diet contains 60 kcal% fat and is deficient in methionine and choline. HFMCD-induced NASH mouse model shows increased liver injury, hepatitic steatosis, and fibrosis accompanied by increased NAS.
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STZ-HFD NASH model
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Neonatal mice injected with Streptozotocin and fed a high fat diet exhibited altered body weight and blood glucose levels.
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GAN Model
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This high fructose and high cholesterol diet-induced NASH model develops obesity, impaired glucose tolerance and hepatic steatosis.
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