Nonalcoholic Steatohepatitis (NASH) Models

NEW!
MSNASH/PcoJ
(030888)

B6.Cg-Lep^ob/J
(000632)

B6.BKS(D)-Lepr^db/J
(000697)

C57BL/6J
(000664)

• MS-NASH is a polygenic mouse model with an intact leptin pathway that develops many of the features associated with metabolic syndrome
• Progression of NASH can be induced via specialized diets with high fat and fructose, resulting in steatosis, inflammation, hepatocellular ballooning, and fibrosis.

• Leptin-deficient ob/ob mice have a genetic predisposition to hyperphagy and obesity.
• Ob/ob mice fed high fat, high cholesterol, and high fructose, and MCD diets exhibit several key NASH features including steatosis and hepatocellular ballooning, but rarely develop significant fibrosis.

• Leptin-resistant db/db mice exhibit similar metabolic features to ob/ob mice, but have normal to elevated levels of leptin.
• In contrast to ob/ob mice, db/db mice fed high calorie and MCD diets often develop moderate to severe liver fibrosis.

• C57BL/6J mice are frequently used in NASH research due to their intrinsic predilection to metabolic syndrome and an intact leptin pathway.
• Mice fed with specialized diets display a number of key NASH phenotypes, however, High fat diet models typically have incomplete penetrance and require a significant amount of time for induction.

B6;129S4-Mc4r^tm1Lowl/J
(006414)

B6.129P2-Apoetm1Unc/J (002052); B6.129S7-Ldlrtm1Her/J (002207)

B6;SJL-Tg(aP2-SREBF1c)9884Reh/J
(003393)

B6.Cg-Ptprc^aMir223^tm1Fcam/J
(013198)

• Mc4r-/- mice exhibit hyperphagic obesity in the context of an intact leptin pathway, resulting in a number of key features that are consistent with metabolic syndrome
• When fed a HFD, these mice have been observed to develop steatosis, inflammation, hepatocellular ballooning, and fibrosis.

• Apoe-/- and Ldlr-/- mice contain genetic mutations in key genes involved with lipoprotein metabolism, resulting in hypercholesterolemia, atherosclerosis, and obesity
• Although traditionally used to study cardiovascular disease, these mice fed NASH-inducing diets develop a number of key features including steatosis, hepatocellular ballooning, inflammation, and fibrosis.

• The SREB-1C gene is involved in glucose metabolism, and the synthesis and uptake of cholesterol, fatty acids, and triglycerides.
• Though the liver histology of this model recapitulate many features of human NASH, it exhibits decreased adipose tissue over time.

• MiR-223 is involved in the differential expression of several key inflammation genes in a number of cell types including neutrophils and hepatocytes.
• MiR-223 -/- have been shown to exhibit steatosis, hepatocellular ballooning, inflammation and fibrosis following induction with high fat diet.