Nonalcoholic Steatohepatitis (NASH)

JAX has the most comprehensive portfolio of NASH mouse models to support your preclinical research needs. Leverage both traditional and novel NASH models to test your unique research questions, and gain confidence in your study results by utilizing the models that are right for you.

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NASH is a complex metabolic disease which can require the use of multiple mouse models to evaluate mechanistic details. Utilize JAX’s expansive portfolio of NASH models to support your research needs and validate key phenotypic endpoints including hepatic steatosis, ballooning, inflammation, and fibrosis.

  Confidently access the right platform for your study, and characterize various phenotypes and readouts.

Popular Models

Name & Stock Number

NEW!
MSNASH/PcoJ
(030888)

B6.Cg-Lepob/J
(000632)

B6.BKS(D)-Leprdb/J
(000697)

C57BL/6J
(000664)

Common Name

MS-NASH

B6 ob; Ob/Ob

B6 db; Db/Db

B6

Genetic Profile

Polygenic

Monogenic

Monogenic

Polygenic

Relative Time to Induction (Scale from 1 to 5)

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 Fructose

Differentiating Features

·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

References

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

Emerging Models

Name & Stock Number

B6;129S4-Mc4rtm1Lowl/J
(006414)

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

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

B6.Cg-PtprcaMir223tm1Fcam/J
(013198)

Common Name

loxTB
Mc4r
Mc4r KO

ApoE KO; Ldlr KO

aP2-SREBP-1c

miR-233-, Mir223 KO

Genetic Profile

Monogenic

Monogenic

Monogenic

Monogenic

Relative Time to Induction (Scale from 1 to 5)

High Fat

High Fat, High Cholesterol

Methionine and Choline Deficient (MCD)

None

High Fat

Methionine Choline Deficient (MCD)

Differentiating Features

·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.

References

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


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