The CIDEB (Cell Death Inducing DFFA Like Effector B) gene encodes a lipid transferase protein that is predominantly expressed in the liver, but also found in significant levels in the small intestine, colon, kidney, and spleen. This protein primarily localizes to the cytosol, perinuclear region of the cytoplasm, and specifically to lipid droplets and the endoplasmic reticulum, where it plays a critical role in lipid metabolism by promoting the fusion of lipid droplets to form larger unilocular droplets, thereby favoring lipid storage and restricting lipolysis ^[1]. CIDEB is also essential for the lipidation and maturation of very-low-density lipoproteins (VLDLs) and chylomicrons, facilitating their transport ^[2]. Beyond lipid metabolism, CIDEB has been implicated in the positive regulation of apoptosis, though its basal expression levels do not typically induce cell death ^[3]. Furthermore, CIDEB influences the replication cycle of hepatitis C virus (HCV) and hepatitis B virus (HBV), acting as a cofactor for HCV entry into hepatocytes ^[4]. Associated diseases include various liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), with rare germline loss-of-function variants in CIDEB demonstrating a protective effect against these liver diseases ^[5]. The huCIDEB(2) mouse is a humanized model generated by cloning the sequence upstream of human CIDEB exon 1 to downstream of exon 5 in reverse orientation into intron 1 of the ROSA26 gene, and simultaneously knocking out mouse Cideb exon 2. huCIDEB(2) mice can be used for research into the pathogenesis of various liver conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV). They are also useful for the screening, development, and safety evaluation of CIDEB-targeted drugs. Cyagen also offers a related model: the huCIDEB(1) Mouse (Catalog No.: C001803). The huCIDEB(1) mouse utilizes a mouse gene in situ replacement strategy, employing the endogenous mouse promoter to drive human CIDEB (covering exon 1 to exon 5). This results in negligible expression of the adjacent gene Ltb4r2 and low levels of human CIDEB mRNA. In contrast, the huCIDEB(2) mouse (Catalog No.: C001990) uses the human promoter to drive the complete human CIDEB sequence including upstream and downstream regulatory regions, thereby preserving normal Ltb4r2 expression and achieving robust human CIDEB mRNA expression.

The huINHBE/huCIDEB(2) mice are a double-gene humanized model obtained by mating huINHBE mice (Catalog Number: C001533) with huCIDEB(2) mice (Catalog Number: C001990). This model is applicable to the study of pathogenesis of various liver diseases, such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), as well as the research on obesity and metabolic diseases associated with improper fat distribution and storage. It can also be used for the screening, development, and preclinical evaluation of INHBE/CIDEB-targeted therapeutics.

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.