H11-Alb-hHSD17B13 Mouse

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.