The ASGR1 Knockout HAP1 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population targeting the ASGR1 gene in HAP1 cells. This loss-of-function model disrupts the major asialoglycoprotein receptor subunit, providing a robust system for studying glycoprotein clearance without clonal selection artifacts inherent in monoclonal lines.
HAP1 is a human near-haploid chronic myeloid leukemia cell line with an adherent, fibroblast-like morphology. Derived from a CML patient, its near-haploid genome facilitates gene editing and functional genomics, enabling unambiguous genotype-phenotype correlations in pathways such as receptor-mediated endocytosis.
ASGR1 encodes the major subunit of the hepatic asialoglycoprotein receptor, which recognizes desialylated glycoproteins and initiates clathrin-mediated endocytosis through interaction with ASGR2 and clathrin adaptors. Trafficking proceeds via EEA1-positive early endosomes to LAMP1-rich lysosomes. The receptor is regulated by HNF4A and CEBPA, with STAT3 modulating its activity. Primary substrates include von Willebrand factor and thrombospondin-1, whose clearance governs JAK2-STAT3 signaling and thrombopoietin homeostasis. ASGR1 also interacts with LRP1, integrating glycoprotein turnover with coagulation regulation.
Loss of ASGR1 in HAP1 cells abolishes the Ashwell-Morell pathway, leading to accumulation of desialylated ligands such as asialoorosomucoid and dysregulation of coagulation factor clearance. This phenotype models key aspects of hepatic processing defects, supporting research on coronary artery disease, dyslipidemia, viral entry (HBV/HCV), and thrombocytopenia. The polyclonal nature captures population-level disruption without clonal adaptation artifacts.
These cells enable fluorescent asialoorosomucoid uptake assays to quantify endocytosis, western blotting and immunofluorescence for ASGR1 expression, and flow cytometry to monitor surface receptor levels. They also support clathrin-mediated internalization and lysosomal degradation assays, coagulation factor ELISA, and platelet binding studies. This knockout model accelerates CRISPR validation and drug target identification in metabolic and cardiovascular indications. For further details, please contact Ascent Research.
