ASGR1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population generated from the AGS human gastric adenocarcinoma line for loss-of-function studies of the ASGR1 gene. This heterogeneous pool avoids clonal artifacts and enables robust bulk assays, including biochemical, transcriptomic, and functional analyses. The polyclonal nature preserves population-level diversity, suitable for experiments where clonal uniformity is not required. The knockout is via CRISPR/Cas9-mediated gene disruption, abolishing the asialoglycoprotein receptor major subunit.
AGS is a gastric adenocarcinoma epithelial cell line with wild-type p53, commonly used in cancer biology, drug testing, and epithelial studies. Its non-hepatic background permits investigation of ASGR1 functions outside the liver, exploring potential roles in gastric epithelial pathophysiology and tumorigenesis.
ASGR1 encodes the HL-1 subunit of the asialoglycoprotein receptor, which dimerizes with ASGR2 to form a calcium-dependent lectin recognizing desialylated glycoproteins. Ligand engagement triggers clathrin-mediated endocytosis through AP2, dynamin, and Rab5-positive endosomes, routing cargo to lysosomes for degradation. This pathway is regulated by liver-enriched transcription factors HNF4A and CEBPA, and it mediates clearance of thrombospondin-1, apoptotic cells, and LDL-cholesterol-modulating glycoproteins. In the knockout, this endocytic clearance axis is disrupted.
Though primarily hepatic, ASGR1 expression in gastric tissues suggests alternative functions. This model allows dissection of its role in epithelial cancer, such as receptor recycling, immune evasion, and lipid metabolism alterations. ASGR1 variants correlate with coronary artery disease and hypercholesterolemia, supporting cardiovascular target studies. Additionally, loss of ASGR1 in cancer cells may influence metabolic signaling.
Applications include fluorescent ligand uptake assays for endocytosis measurement, flow cytometry for receptor surface expression, western blot/RT-qPCR for validation, and RNA-seq or lipid profiling for global changes. Apoptosis assays and ASGPR-targeted drug delivery testing are also enabled. The polyclonal population is ideal for functional screens and experiments needing genetic diversity. Please contact Ascent Research for details.