The ASGR1 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the human pancreatic ductal adenocarcinoma cell line PaTu 8988t, with targeted disruption of the ASGR1 gene. This loss-of-function model enables study of the asialoglycoprotein receptor in a metastatic cancer background that lacks endogenous ASGR1 expression. The product provides a heterogeneous edited pool suitable for population-level analyses.
PaTu 8988t cells were derived from a liver metastasis of a pancreatic ductal adenocarcinoma and carry KRAS G12V and TP53 mutations, establishing a model of aggressive, metastatic disease. These cells do not endogenously express ASGR1, making the knockout an ideal control for ectopic expression and complementation experiments. The polyclonal format avoids clonal selection bias and facilitates bulk functional studies.
ASGR1 is a C-type lectin receptor that recognizes terminal galactose or N-acetylgalactosamine residues on desialylated glycoproteins, initiating clathrin-dependent endocytosis via interaction with ASGR2 and the AP2 adaptor complex. Internalized cargo progresses through rab5- and EEA1-positive early endosomes to lysosomal degradation by lysosomal hydrolases. Transcriptionally, ASGR1 is regulated by HNF4A and insulin/STAT3 signaling, while its endocytic activity can modulate downstream JAK2/STAT3 pathways. The receptor??s trafficking also involves caveolin-1, suggesting alternative endocytic routes.
In pancreatic cancer, ASGR1??s role remains largely unexplored. The knockout in PaTu 8988t provides a defined null background for dissecting non-hepatic functions, such as potential effects on tumor cell signaling or metastasis. It also serves as a comparator for hepatic ASGR1 studies in cardiovascular disease and viral hepatitis B entry. The polyclonal population is well-suited for drug delivery research and functional genomics screens.
Applications include ASGR1 functional characterization, endocytosis assays using asialo-orosomucoid, and validation of gene disruption via western blotting and RT-qPCR. The cells support ligand uptake studies, immunofluorescence, flow cytometry, and proliferation/apoptosis analysis. They are also applicable to drug sensitivity screening and as a control for liver-cell models. Contact Ascent Research for further details.
