H11-Alb-hHSD17B13 Mice

Catalog Number: I001192

Strain Name: C57BL/6JCya-Igs2em1(Alb-hHSD17B13)/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

 

Strain Description

17β-hydroxysteroid dehydrogenase 13 (HSD17B13) is a liver-enriched lipid droplet (LD)-associated protein that catalyzes the interconversion between 17-ketosteroids and 17-hydroxysteroids. HSD17B13 protein is selectively expressed in liver cells and localizes exclusively to the surface of lipid droplets, with similar tissue distribution and subcellular localization observed in both humans and mice [1]. HSD17B13 may play a significant role in regulating the biogenesis, growth, and degradation of lipid droplets in the liver. Metabolic-associated fatty liver disease (MAFLD) is pathologically defined by abnormal accumulation of neutral lipids (such as triglycerides and cholesterol esters) within hepatocellular lipid droplets. Its inflammatory form, metabolic-associated steatohepatitis (MASH), is closely associated with the pathogenesis of chronic liver diseases. Research has found that HSD17B13 protein expression is markedly elevated in the livers of MAFLD patients compared to healthy individuals [2-3]. Abnormal expression and dysfunction of HSD17B13 may be one of the pathogenic mechanisms of chronic liver disease, particularly in the MAFLD. As a potential therapeutic target for MAFLD and MASH, there are currently clinical-stage drug pipelines targeting the HSD17B13 gene, including ASO drug ION-455 developed by Ionis and siRNA drug Rapirosiran developed by Regeneron Pharmaceuticals.

The H11-Alb-hHSD17B13 mouse model is generated by integrating the human HSD17B13 protein coding region (CDS) into the mouse H11 safe harbor locus. The human HSD17B13 gene is specifically expressed in the liver under the regulation of the mouse Alb promoter. This model can be used to study the pathogenic mechanisms of the HSD17B13 gene in metabolic-associated fatty liver disease (MAFLD) and related chronic liver diseases, as well as for evaluating targeted drug development.

Strain Strategy

The "Alb promoter-Kozak-Human HSD17B13 CDS-WPRE-BGH pA" cassette was inserted into the H11 locus (Approx 0.7 kb upstream of the Eif4enif1 gene and 4.5 kb downstream of the Drg1 gene).


Application

  • Research on metabolism-associated fatty liver disease (MAFLD), metabolism-associated steatohepatitis (MASH), and other chronic liver diseases;
  • Preclinical evaluation of HSD17B13-targeted drugs.

 

Validation Data

1. Detection of human HSD17B13 gene expression


Figure 1. Human HSD17B13 gene expression in the duodenum and liver of 6-week-old male H11-Alb-hHSD17B13 mice and wild-type (WT) mice. RT-qPCR results demonstrate significant expression of the human HSD17B13 gene in the duodenum and liver of H11-Alb-hHSD17B13 mice, whereas wild-type mice do not express the human HSD17B13 gene in these tissues.

2. Detection of human HSD17B13 protein expression


Figure 2. Western blot analysis of human HSD17B13 protein (hHSD17B13) expression in the liver of 6-week-old male H11-Alb-hHSD17B13 mice and wild-type (WT) mice*. The results demonstrate significant expression of human HSD17B13 protein in the liver of H11-Alb-hHSD17B13 mice, whereas wild-type mice do not express human HSD17B13 protein in their liver.

*The recombinant Anti-HSD17B13 antibody used for this assay is purchased from Abcam, with product number ab316153.

 

References
[1]Zhang HB, Su W, Xu H, Zhang XY, Guan YF. HSD17B13: A Potential Therapeutic Target for NAFLD. Front Mol Biosci. 2022 Jan 7;8:824776.
[2]Su W, Wang Y, Jia X, Wu W, Li L, Tian X, Li S, Wang C, Xu H, Cao J, Han Q, Xu S, Chen Y, Zhong Y, Zhang X, Liu P, Gustafsson JÅ, Guan Y. Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11437-42.
[3]Ma Y, Belyaeva OV, Brown PM, Fujita K, Valles K, Karki S, de Boer YS, Koh C, Chen Y, Du X, Handelman SK, Chen V, Speliotes EK, Nestlerode C, Thomas E, Kleiner DE, Zmuda JM, Sanyal AJ; (for the Nonalcoholic Steatohepatitis Clinical Research Network); Kedishvili NY, Liang TJ, Rotman Y. 17-Beta Hydroxysteroid Dehydrogenase 13 Is a Hepatic Retinol Dehydrogenase Associated With Histological Features of Nonalcoholic Fatty Liver Disease. Hepatology. 2019 Apr;69(4):1504-1519.