huMTARC1/huMTARC2/huCIDEB(2) Mouse
Product Name
huMTARC1/huMTARC2/huCIDEB(2) Mouse
Product ID
C002062
Strain Name
C57BL/6N;6JCya-Mtarc1tm1(hMTARC1)Mtarc2tm1(hMTARC2)Cidebem1Gt(ROSA)26Sortm1(hCIDEB)/Cya
Backgroud
C57BL/6N;6JCya
Status
When using this mouse strain in a publication, please cite “huMTARC1/huMTARC2/huCIDEB(2) Mouse (Catalog C002062) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CIDEB & MTARC2 & MTARC1
Gene Alias
MARC2, MOSC2, MARC1, MOSC1
NCBI ID
Chromosome
Chr 14 (Human), Chr 1 (Human), Chr 1 (Human)
MGI ID
Datasheet
Strain Description
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 simultaneously carries the humanized MTARC1, MTARC2, and CIDEB targets and can be used for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of multitarget therapeutics targeting MTARC1/MTARC2/CIDEB, as well as studies on hepatic lipid metabolism regulation, mitochondrial redox homeostasis, and lipid droplet dynamics. It also serves as 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.
Reference
Struwe MA, Scheidig AJ, Clement B. The mitochondrial amidoxime reducing component-from prodrug-activation mechanism to drug-metabolizing enzyme and onward to drug target. J Biol Chem. 2023 Nov;299(11):105306.
Guo Y, Gao Z, LaGory EL, Kristin LW, Gupte J, Gong Y, Rardin MJ, Liu T, Nguyen TT, Long J, Hsu YH, Murray JK, Lade J, Jackson S, Zhang J. Liver-specific mitochondrial amidoxime-reducing component 1 (Mtarc1) knockdown protects the liver from diet-induced MASH in multiple mouse models. Hepatol Commun. 2024 May 2;8(5):e0419.
Hou W, Watson C, Cecconie T, Bolaki MN, Brady JJ, Lu Q, Gatto GJ Jr, Day TA. Biochemical and functional characterization of the p.A165T missense variant of mitochondrial amidoxime-reducing component 1. J Biol Chem. 2024 Jun;300(6):107353.
Coyne ES, Nie Y, Lee D, Pandovski S, Yang T, Zhou H, Rosahl TW, Carballo-Jane E, Abdurrachim D, Zhou Y, Hendra C, Ali AAB, Meyers S, Blumenschein W, Gongol B, Liu Y, Zhou Y, Talukdar S. Loss of mitochondrial amidoxime-reducing component 1 (mARC1) prevents disease progression by reducing fibrosis in multiple mouse models of chronic liver disease. Hepatol Commun. 2025 Feb 10;9(2):e0637.
Lewis LC, Chen L, Hameed LS, Kitchen RR, Maroteau C, Nagarajan SR, Norlin J, Daly CE, Szczerbinska I, Hjuler ST, Patel R, Livingstone EJ, Durrant TN, Wondimu E, BasuRay S, Chandran A, Lee WH, Hu S, Gilboa B, Grandi ME, Toledo EM, Erikat AHA, Hodson L, Haynes WG, Pursell NW, Coppieters K, Fleckner J, Howson JMM, Andersen B, Ruby MA. Hepatocyte mARC1 promotes fatty liver disease. JHEP Rep. 2023 Feb 3;5(5):100693.
Xu L, Li L, Wu L, Li P, Chen FJ. CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth. FEBS Lett. 2024 May;598(10):1154-1169.
Ye J, Li JZ, Liu Y, Li X, Yang T, Ma X, Li Q, Yao Z, Li P. Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab. 2009 Feb;9(2):177-90.
Wu X, Lee EM, Hammack C, Robotham JM, Basu M, Lang J, Brinton MA, Tang H. Cell death-inducing DFFA-like effector b is required for hepatitis C virus entry into hepatocytes. J Virol. 2014 Aug;88(15):8433-44.
Strain Strategy
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).
Figure 1. Gene editing strategy for huMTARC1/huMTARC2 mice. The sequences from upstream of exon 1 of the mouse Mtarc2 gene to downstream of exon 7 of the mouse Mtarc1 gene were replaced with the sequences from upstream of exon 1 of the human MTARC2 gene to downstream of exon 7 of the human MTARC1 gene. The expression of mouse Mir1981 will be affected by the deletion of this KO region.
Figure 2. Gene editing strategy of huCIDEB(2) mice. The sequence from upstream of exon 1 of the human CIDEB gene to downstream of exon 5 of the human CIDEB gene was cloned into intron 1 of ROSA26 in reverse orientation. The Cideb gene contains five exons, with the start codon located in exon 1 and the stop codon located in exon 5. The coding region of exon 2 was selected as the target site.
Application Area
Screening, pharmacodynamic evaluation, safety evaluation, and mechanism of action research of multi - target drugs targeting MTARC1/MTARC2/CIDEB;
Research on the mechanisms of liver lipid metabolism regulation, mitochondrial redox homeostasis, and lipid droplet dynamics;
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.
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