huMTARC1/huMTARC2/huCIDEB(2) Mouse

Mitochondrial amidoxime reducing components 1 and 2 (MTARC1 and MTARC2) encode the molybdenum-containing enzymes mARC1 and mARC2, respectively, which are localized to the outer mitochondrial membrane. Together with cytochrome b5 (CYB5B) and NADH-cytochrome b5 reductase 3 (CYB5R3), they constitute the mitochondrial reducing system and participate in the reduction of N-oxygenated compounds, drug metabolism, nitric oxide homeostasis, lipid metabolism regulation, and mitochondrial redox homeostasis ^[1-3]. Recent studies have demonstrated that protective variants or functional inhibition of MTARC1 reduce hepatic lipid accumulation, inflammation, and fibrosis, and significantly decrease the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and other liver diseases, making MTARC1 a promising therapeutic target for the treatment of MASLD/MASH ^[4-5]. The CIDEB (cell death-inducing DFFA-like effector B) gene encodes a lipid transfer protein localized to lipid droplets and the endoplasmic reticulum. By promoting lipid droplet fusion and regulating very-low-density lipoprotein (VLDL) assembly and lipid storage, CIDEB plays a critical role in maintaining hepatic lipid homeostasis ^[6-7]. Studies have shown that loss of CIDEB function reduces the risk of multiple liver diseases, including MASLD, MASH, liver cirrhosis, and viral hepatitis ^[8]. MTARC1/MTARC2-mediated mitochondrial redox metabolism and CIDEB-mediated lipid droplet dynamics and lipid storage jointly participate in the regulation of hepatocellular lipid metabolism through two key processes, namely lipid oxidation/utilization and lipid storage, thereby coordinately influencing hepatic lipid homeostasis, oxidative stress, and disease progression, providing new insights into combination intervention strategies for metabolism-related liver diseases, such as MASLD and MASH.

The huMTARC1/huMTARC2/huCIDEB(2) mouse is a triple-gene humanized model generated by crossing the huMTARC1/huMTARC2 mouse (Catalog No.: C001912) with the huCIDEB(2) mouse (Catalog No.: C001990). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of multi-target drugs targeting MTARC1/MTARC2/CIDEB, as well as mechanistic studies on hepatic lipid metabolism regulation, mitochondrial redox homeostasis, and lipid droplet dynamics. It provides an ideal preclinical research platform for the development of innovative therapies for metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and other metabolism-related liver diseases.