B6-hGDF15 Mouse
Product Name
B6-hGDF15 Mouse
Product ID
C001520
Strain Name
C57BL/6JCya-Gdf15em1(hGDF15)/Cya
Backgroud
C57BL/6JCya
When using this mouse strain in a publication, please cite “B6-hGDF15 Mouse (Catalog C001520) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
PDF, MIC1, PLAB, MIC-1, NAG-1, PTGFB, GDF-15
NCBI ID
Chromosome
Chr 19
MGI ID
Datasheet
Strain Description
The Growth Differentiation Factor 15 (GDF15) gene encodes a secreted ligand of the Transforming Growth Factor-β (TGF-β) superfamily protein. This protein plays a crucial role in the TGFβ signaling pathway, which is integral to various cellular processes [1]. GDF15 is involved in the body’s response to stress following cell damage. It is associated with tissue hypoxia, inflammation, acute injury, and oxidative stress, among other disease states. Elevated levels of GDF15 in the serum are considered a potential biomarker for the progression of cancer, as it is overexpressed in various types of tumor cells, including colon, prostate, pancreatic, breast, and thyroid cancers [2-3]. Interestingly, GDF15 is not solely a pathological biomarker. Despite its association with disease states, it also exhibits high expression under various non-pathological conditions. Studies suggest that GDF15 may exert a protective effect on the heart, liver, kidney, and lungs following inflammation and injury, highlighting its potential role in tissue repair and recovery [4].
GDF15 is an important biomarker for metabolic diseases, cardiovascular diseases, tumors, and more, and holds potential as a therapeutic target. It can induce anorexia by activating the GFRAL-RET receptor in the brainstem, making it a promising target for anti-obesity therapy [5]. Furthermore, GDF15 neutralization could potentially alleviate anorexia and weight loss, common side effects of platinum-based chemotherapy [6]. Research has shown that a therapeutic antagonistic monoclonal antibody can inhibit RET signal transduction by blocking the interaction between GDF15-driven RET and cell surface GFRAL. This could reverse excessive lipid oxidation in tumor-bearing mice and prevent cancer cachexia [7]. The potential of GDF15 as a therapeutic target is being increasingly recognized in the scientific community. In this context, the construction of animal gene humanization models for this target is of significant importance, providing a crucial tool for further research and development in this area.
This strain is a mouse Gdf15 gene humanized model expressing human GDF15 protein obtained by replacing the sequence encoding the endogenous structural domain in the mouse Gdf15 gene with the sequence encoding the structural domain in the human GDF15 gene. B6-hGDF15 mice can be used for research on metabolic diseases, cardiovascular diseases, tumor occurrence and development, etc., to assist in the preclinical evaluation of GDF15-targeted drugs.
Reference
Assadi A, Zahabi A, Hart RA. GDF15, an update of the physiological and pathological roles it plays: a review. Pflugers Arch. 2020 Nov;472(11):1535-1546.
Breit SN, Johnen H, Cook AD, Tsai VW, Mohammad MG, Kuffner T, Zhang HP, Marquis CP, Jiang L, Lockwood G, Lee-Ng M, Husaini Y, Wu L, Hamilton JA, Brown DA. The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors. 2011 Oct;29(5):187-95.
Bauskin AR, Brown DA, Kuffner T, Johnen H, Luo XW, Hunter M, Breit SN. Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 2006 May 15;66(10):4983-6.
Emmerson PJ, Duffin KL, Chintharlapalli S, Wu X. GDF15 and Growth Control. Front Physiol. 2018 Nov 27;9:1712.
Borner T, Shaulson ED, Ghidewon MY, Barnett AB, Horn CC, Doyle RP, Grill HJ, Hayes MR, De Jonghe BC. GDF15 Induces Anorexia through Nausea and Emesis. Cell Metab. 2020 Feb 4;31(2):351-362.e5.
Breen DM, Kim H, Bennett D, Calle RA, Collins S, Esquejo RM, He T, Joaquim S, Joyce A, Lambert M, Lin L, Pettersen B, Qiao S, Rossulek M, Weber G, Wu Z, Zhang BB, Birnbaum MJ. GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates. Cell Metab. 2020 Dec 1;32(6):938-950.e6.
Suriben R, Chen M, Higbee J, Oeffinger J, Ventura R, Li B, Mondal K, Gao Z, Ayupova D, Taskar P, Li D, Starck SR, Chen HH, McEntee M, Katewa SD, Phung V, Wang M, Kekatpure A, Lakshminarasimhan D, White A, Olland A, Haldankar R, Solloway MJ, Hsu JY, Wang Y, Tang J, Lindhout DA, Allan BB. Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. Nat Med. 2020 Aug;26(8):1264-1270.
Strain Strategy
The mouse Gdf15 endogenous domain was replaced with the human GDF15 domain. The murine signal peptide was remained.
Figure 1. Gene editing strategy of B6-hGDF15 mice.
Application Area
Research on cardiovascular diseases such as heart disease;
Research on metabolic diseases such as diabetes and anorexia;
Research on colorectal cancer, prostate cancer, and other cancers;
Preclinical evaluation of GDF15-targeted drugs.
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