The ASGR1 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-mediated gene-disrupted cell population generated from the SK-HEP-1 human cell line. This polyclonal knockout model provides a loss-of-function system for investigating the biological roles of the ASGR1 gene, which encodes a subunit of the asialoglycoprotein receptor. The product is supplied as a heterogeneous pool of edited cells, reflecting the polyclonal knockout format, and is intended for use in experiments that require ablation of ASGR1 function without clonal selection.
The host cell line SK-HEP-1 was originally derived from ascites of a hepatic adenocarcinoma patient and displays a well-characterized endothelial phenotype. Functionally, SK-HEP-1 cells model liver sinusoidal endothelial cells, which play critical roles in maintaining the endothelial barrier, scavenging macromolecules from the circulation, and modulating immune responses. This unique cellular background makes SK-HEP-1 particularly valuable for studying endothelial biology and hepatic clearance mechanisms in a human context.
ASGR1 encodes the major subunit of the asialoglycoprotein receptor, which mediates clathrin-dependent endocytosis and lysosomal degradation of desialylated glycoproteins. The receptor forms a heterodimer with ASGR2 and interacts with the AP2 adaptor complex and clathrin to trigger internalization. Upon ligand binding, the complex is trafficked through early endosomes to lysosomes, where lysosomal proteases degrade the cargo, maintaining glycoprotein homeostasis. Transcription of ASGR1 is regulated by HNF4A, FOXA2, and glucocorticoid receptor signaling. Calcium ions are essential for ligand binding, and key downstream events include clathrin coat assembly and degradation of desialylated glycoproteins.
In the SK-HEP-1 endothelial background, ASGR1 knockout disrupts hepatic glycoprotein clearance and provides insight into endothelial function. This model is relevant for studying cardiovascular disease and dyslipidemia, as ASGR1 influences plasma levels of clearance targets. Moreover, ASGR1’s involvement in hepatitis C virus entry and liver fibrosis makes this knockout valuable for pathogen?Chost interaction and fibrosis research. The endothelial phenotype of SK-HEP-1 also allows exploration of sinusoidal barrier and scavenging functions.
Research applications include asialoorosomucoid uptake assays, Western blotting, RT-qPCR, immunofluorescence, and flow cytometry to assess receptor trafficking and function. These cells enable cardiovascular disease modeling, study of hepatitis C virus entry, and investigations into liver sinusoidal endothelial cell biology. The loss-of-function system facilitates detailed analysis of clathrin-mediated endocytosis pathways. For further information, contact Ascent Research.
