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huMTARC1/huMTARC2
製品ID :
C001912
系統:
C57BL/6NCya
状況:
説明:
MTARC1 and MTARC2 encode the mitochondrial amidoxime-reducing components 1 and 2 (mARC1/mARC2), two paralogous molybdenum-containing enzymes anchored to the outer mitochondrial membrane that form a three-component system with cytochrome b5 (CYB5B) and NADH-cytochrome b5 reductase 3 (CYB5R3) to catalyze the reduction of N-oxygenated compounds [1]. These genes are widely expressed, with particularly high levels in liver hepatocytes, as well as in other tissues like adipose and various fetal/adult organs; the encoded proteins function primarily in N-reduction of substrates including amidoximes (for prodrug activation), nitrite, Nω-hydroxy-L-arginine (NOHA), N-hydroxyurea, and hydrogen peroxide, contributing to detoxification, nitric oxide homeostasis, lipid metabolism regulation, and mitochondrial redox balance [2-3]. MTARC1 has gained significant attention due to a common protective missense variant (p.A165T) strongly associated with reduced liver fat, lower plasma lipids and liver enzymes (e.g., ALT), decreased risk of metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), all-cause cirrhosis, and liver-related mortality; genetic and experimental knockdown of MTARC1 in hepatocytes reduces steatosis, fibrosis, and inflammation in mouse models, positioning mARC1 inhibition (e.g., via liver-specific siRNA) as a promising therapeutic strategy for MASH [4-5]. MTARC2 shares overlapping substrate specificities and roles but appears less central to the liver disease associations compared to MTARC1 [6].
The huMTARC1/huMTARC2 mouse is a dual-gene humanized model generated via gene editing. 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. This model is applicable for evaluating drug efficacy in MASLD/MASH, elucidating mechanisms of hepatic lipid metabolism, conducting PK/PD and reductase activity studies, and facilitating the development of MTARC1/MTARC2-targeted therapeutics.
MTARC1 and MTARC2 encode the mitochondrial amidoxime-reducing components 1 and 2 (mARC1/mARC2), two paralogous molybdenum-containing enzymes anchored to the outer mitochondrial membrane that form a three-component system with cytochrome b5 (CYB5B) and NADH-cytochrome b5 reductase 3 (CYB5R3) to catalyze the reduction of N-oxygenated compounds [1]. These genes are widely expressed, with particularly high levels in liver hepatocytes, as well as in other tissues like adipose and various fetal/adult organs; the encoded proteins function primarily in N-reduction of substrates including amidoximes (for prodrug activation), nitrite, Nω-hydroxy-L-arginine (NOHA), N-hydroxyurea, and hydrogen peroxide, contributing to detoxification, nitric oxide homeostasis, lipid metabolism regulation, and mitochondrial redox balance [2-3]. MTARC1 has gained significant attention due to a common protective missense variant (p.A165T) strongly associated with reduced liver fat, lower plasma lipids and liver enzymes (e.g., ALT), decreased risk of metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), all-cause cirrhosis, and liver-related mortality; genetic and experimental knockdown of MTARC1 in hepatocytes reduces steatosis, fibrosis, and inflammation in mouse models, positioning mARC1 inhibition (e.g., via liver-specific siRNA) as a promising therapeutic strategy for MASH [4-5]. MTARC2 shares overlapping substrate specificities and roles but appears less central to the liver disease associations compared to MTARC1 [6].
The huMTARC1/huMTARC2 mouse is a dual-gene humanized model generated via gene editing. 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. This model is applicable for evaluating drug efficacy in MASLD/MASH, elucidating mechanisms of hepatic lipid metabolism, conducting PK/PD and reductase activity studies, and facilitating the development of MTARC1/MTARC2-targeted therapeutics.
huMTARC1/huMTARC2/huCIDEB(2)
製品ID :
C002062
系統:
C57BL/6N;6JCya
状況:
説明:
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.
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.
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