huGDF8/huALK7/huINHBE Mouse
제품명
huGDF8/huALK7/huINHBE Mouse
제품 ID
C002082
품종 계통
C57BL/6NCya-Mstnem1(hMSTN)Acvr1ctm1(hACVR1C)Inhbetm1(hINHBE)/Cya
Backgroud
C57BL/6NCya
상태
이 마우스 계통을 논문에서 사용할 경우, “huGDF8/huALK7/huINHBE Mouse (카탈로그 번호 C002082)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
구매 가능한 제품 종류
연령
Genotype
성별
수량
유전자 별칭
ALK7, ACVRLK7, GDF8, MSLHP
염색체
Chr 2, Chr 2, Chr 12
MGI ID
Datasheet
품종 계통 설명
Growth differentiation factor 8 (GDF8) is a key negative regulator of skeletal muscle growth that inhibits the proliferation and differentiation of muscle cells and maintains muscle mass homeostasis [1-4]. Activin receptor-like kinase 7 (ALK7, ACVR1C) is a type I receptor of the transforming growth factor-β (TGF-β) superfamily. It is widely expressed in adipose tissue and metabolically active organs and participates in the regulation of adipogenesis, energy metabolism, and glucose homeostasis [5-6]. Inhibin beta E subunit (INHBE) is a liver-specific member of the TGF-β superfamily. The Activin E encoded by INHBE functions as a hepatokine that plays an important role in maintaining metabolic homeostasis by regulating lipid storage, adipose tissue function, and systemic energy metabolism [7]. Recent studies have further demonstrated that the INHBE-ALK7 signaling axis participates in the metabolic regulation between the liver and adipose tissue, and its dysregulation is closely associated with metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD) [8]. Meanwhile, GDF8-mediated regulation of skeletal muscle mass is extensively interconnected with adipose and hepatic metabolism [9-10]. GDF8, INHBE, and ALK7 each participate in the metabolic regulation among these tissues and collectively influence whole-body energy homeostasis, fat distribution, and glucose metabolism, providing new insights into combination intervention strategies for promoting muscle growth, reducing adiposity, and improving metabolic health.
The huGDF8/huALK7/huINHBE mouse is a triple-gene humanized model that can be generated by intercrossing the huMSTN(GDF8) mouse (Catalog No.: C001636), the huALK7(ACVR1C) mice (Catalog No.: C001911) and the huINHBE mice (Catalog No.: C001533). This model simultaneously carries the humanized GDF8, ACVR1C, and INHBE genes and can be used for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting GDF8, ACVR1C, and INHBE, as well as studies on body composition remodeling, regulation of the muscle-adipose-liver metabolic axis, and energy metabolic reprogramming. It also serves as a preclinical research platform for developing combination therapeutic strategies for promoting muscle growth, reducing adiposity, and improving metabolic health, as well as innovative therapies for metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD).
Reference
Chen MM, Zhao YP, Zhao Y, Deng SL, Yu K. Regulation of Myostatin on the Growth and Development of Skeletal Muscle. Front Cell Dev Biol. 2021 Dec 24;9:785712.
Yang M, Liu C, Jiang N, Liu Y, Luo S, Li C, et al. Myostatin: a potential therapeutic target for metabolic syndrome. Front Endocrinol. 2023;14:1181913.
Lee SJ. Targeting the myostatin signaling pathway to treat muscle loss and metabolic dysfunction. J Clin Invest. 2021 May 3;131(9):e148372.
Wang H, Guo S, Gao H, Ding J, Li H, Kong X, Zhang S, He M, Feng Y, Wu W, Xu K, Chen Y, Zhang H, Liu T, Kong X. Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication. J Clin Invest. 2024 Jun 18;134(16):e178303
Ibáñez CF. Regulation of metabolic homeostasis by the TGF-β superfamily receptor ALK7. FEBS J. 2022 Oct;289(19):5776-5797.
Zhao M, Okunishi K, Bu Y, Kikuchi O, Wang H, Kitamura T, Izumi T. Targeting activin receptor-like kinase 7 ameliorates adiposity and associated metabolic disorders. JCI Insight. 2023 Feb 22;8(4):e161229.
Griffin JD, Buxton JM, Culver JA, Barnes R, Jordan EA, White AR, Flaherty SE, Bernardo B, Ross T, Bence KK, Birnbaum MJ. Hepatic Activin E mediates liver-adipose inter-organ communication, suppressing adipose lipolysis in response to elevated serum fatty acids. Mol Metab. 2023 Dec;78:101830. doi: 10.1016/j.molmet.2023.101830.
Park SY, Cho Y, Son SM, Hur JH, Kim Y, Oh H, Lee HY, Jung S, Park S, Kim IY, Lee SJ, Choi CS. Activin E is a new guardian protecting against hepatic steatosis via inhibiting lipolysis in white adipose tissue. Exp Mol Med. 2025 Feb;57(2):466-477. doi: 10.1038/s12276-025-01403-6.
Wang H, Guo S, Gao H, Ding J, Li H, Kong X, Zhang S, He M, Feng Y, Wu W, Xu K, Chen Y, Zhang H, Liu T, Kong X. Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication. J Clin Invest. 2024 Jun 18;134(16):e178303.
Marjot T, Armstrong MJ, Stine JG. Skeletal muscle and MASLD: Mechanistic and clinical insights. Hepatol Commun. 2025 May 23;9(6):e0711.
변형 전략
The huGDF8/huALK7/huINHBE mouse is a triple-gene humanized model that can be generated by intercrossing the huMSTN(GDF8) mouse (Catalog No.: C001636), the huALK7(ACVR1C) mice (Catalog No.: C001911), and the huINHBE mice (Catalog No.: C001533).
Figure 1. Gene editing strategy of huMSTN(GDF8) mice. The mouse Mstn genomic DNA was replaced with the human MSTN genomic DNA. The murine signal peptide was preserved.
Figure 2. Gene editing strategy of huALK7(ACVR1C) mice. The sequences from 5’UTR to downstream of 3’UTR of mouse Acvr1c gene were replaced with the sequences from 5’UTR to downstream of 3’UTR of human ACVR1C gene.
Figure 3. Gene editing strategy of huINHBE mice. The sequences from the ATG start codon to the 3'UTR of mouse Inhbe were replaced with the sequences from the ATG start codon to the 3'UTR of human INHBE.
응용 분야
Research on the screening, pharmacodynamic evaluation, safety evaluation, and mechanism of action of drugs targeting three targets: GDF8, ACVR1C, and INHBE;
Combined treatment strategies for fat reduction, muscle gain, and metabolic improvement;
Innovative therapies for metabolic-related diseases, such as obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD).
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