Metabolic Dysfunction-Associated Steatohepatitis (MASH)

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MSNASH/PcoJ
(030888)

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

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

C57BL/6J
(000664)

MS-NASH

B6 ob; Ob/Ob

B6 db; Db/Db

B6

Polygenic

Monogenic

Monogenic

Polygenic

High Fat, High Cholesterol, and High Fructose

High Fat, High Cholesterol, and High Fructose

Methionine and Choline Deficient (MCD)

High Calorie

Methionine and Choline Deficient (MCD)

High Fat, High Cholesterol, and High Fructose

Methionine and Choline Deficient (MCD)

STZ + High Fat

·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 by feeding with an obesogenic diet, 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 obesogenic 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 specialized diets display a number of key NASH phenotypes, however, obesogenic models typically have incomplete penetrance and require a significant amount of time for induction

Sun G et al., 2019; Boland ML et al., 2018

Van Herck MA et al., 2017; Denk H et al., 2019; Lau JK et al., 2017; Mann JP et al., 2016; Hansen HH et al., 2017; Bertola A, 2018; Kristiansen MN et al., 2016; Sahai A et al., 2004

Van Herck MA et al., 2017; Denk H et al., 2019; Ibrahim SH et al., 2016; Mann JP et al., 2016; Hansen HH et al., 2017; Bertola A, 2018; Trak-Smayra V et al., 2011; Wortham M et al., 2008

Van Herck MA et al., 2017; Denk H et al., 2019; Lau JK et al., 2017; Ibrahim SH et al., 2016; Hansen HH et al., 2017; Bertola A, 2018

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)

loxTB
Mc4r
Mc4r KO

ApoE KO; Ldlr KO

aP2-SREBP-1c

miR-233-, Mir223 KO

Monogenic

Monogenic

Monogenic

Monogenic

High Fat

High Fat, High Cholesterol

Methionine and Choline Deficient (MCD)

None

High Fat

Methionine Choline Deficient (MCD)

·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 High Fat Diet, 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.

Mann JP et al., 2016; Itoh M et al., 2011

Hansen HH et al., 2017; Schierwagen R, et al, 2015; Gupte AA et al., 2010; Bieghs V et al., 2012

Denk H et al., 2019; Ip M et al., 2003; Abdelmegeed MA et al., 2011

He et al., 2019