The Mdk Knockout Hepa 1-6 Cell Line is a CRISPR/Cas9-mediated loss-of-function model in which the gene encoding Midkine (Mdk) has been disrupted in the Hepa 1-6 murine hepatoma cell line. This engineered cell line provides a stable knockout background for investigating the role of the secreted heparin-binding growth factor Midkine in hepatocellular carcinoma and related biological processes. The product is supplied as a validated cell line suitable for a wide range of cell-based assays and functional studies.
The parental Hepa 1-6 cell line was originally derived from a C57L/J mouse hepatoma and retains key characteristics of hepatic epithelial cells, including the capacity for metabolism, detoxification, and protein synthesis. Widely used as a model for hepatoma biology, Hepa 1-6 cells exhibit tumorigenic properties in syngeneic hosts and respond to hepatotropic stimuli, making them a relevant platform for liver cancer research. The Mdk knockout in this cell line thus enables dissection of Midkine-dependent pathways in a liver-specific tumor context.
Midkine functions as a pleiotropic cytokine that engages multiple receptors and co-receptors, including protein tyrosine phosphatase receptor type Z1 (PTPRZ1), anaplastic lymphoma kinase (ALK), integrins (ITGA4/ITGB1, ITGA6/ITGB1), low-density lipoprotein receptor-related protein 1 (LRP1), and syndecans (SDC1, SDC2). Upon ligand binding, MDK activates downstream signaling cascades such as the PI3K/AKT axis, the MAPK/ERK cascade, JAK/STAT, and NF-??B pathways, thereby promoting cell proliferation, survival, migration, and angiogenesis. Key upstream regulators that control Mdk expression include NF-??B, STAT3, HIF-1??, TNF-??, and IL-1??, while major downstream effectors include AKT, ERK1/2, SRC, FAK, BCL2, and CCND1.
In the context of Hepa 1-6 hepatoma cells, MDK knockout disrupts the autocrine and paracrine growth factor signaling that drives hepatocellular carcinoma progression. Loss of Midkine impairs activation of the PI3K/AKT and MAPK/ERK pathways, leading to reduced proliferation, enhanced apoptosis, and diminished invasive capacity. This knockout model is therefore invaluable for dissecting Midkine??s contribution to hepatoma malignancy, including its role in tumor-stromal interactions and modulation of the tumor microenvironment. It also serves as a platform for evaluating therapeutic strategies that target Midkine-dependent signaling nodes.
Typical research applications encompass the study of liver cancer progression, investigation of Midkine signaling in hepatoma cells, functional analysis of MDK within the tumor microenvironment, and assessment of Mdk knockout effects on metastasis and drug sensitivity. Researchers can employ a battery of downstream assays, including western blotting for total and phosphorylated AKT and ERK, RT-qPCR for transcriptional targets, cell proliferation assays, Transwell migration and invasion assays, apoptosis detection by flow cytometry or caspase activation, and in vivo xenograft tumor growth studies to monitor tumorigenic potential. For technical inquiries or custom service requests, please contact Ascent Research.
