AGL Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human AGL gene. This product comprises a heterogeneous pool of HAP1 cells carrying diverse gene disruptions, enabling robust loss-of-function studies of glycogen debranching enzyme. The polyclonal format avoids clonal artifacts and preserves population-level phenotypic consistency.
HAP1 cells are a fibroblast-like, near-haploid line derived from a chronic myeloid leukemia patient. Their near-haploid karyotype simplifies genetic knockout by requiring modification of a single allele, and they maintain functional metabolic and signaling pathways. HAP1 cells are widely used for modeling human diseases due to their rapid growth, transfectability, and suitability for high-throughput screening.
The AGL gene encodes a bifunctional glycogen debranching enzyme with transferase and glucosidase activities. During glycogenolysis, glycogen phosphorylase removes ??-1,4-linked glucose residues until blocked at ??-1,6 branch points. AGL then transfers the terminal trisaccharide and cleaves the ??-1,6 bond, releasing free glucose. This process is stimulated by glucagon and epinephrine, which activate cAMP-dependent signaling. AGL cooperates with glycogen phosphorylase and phosphoglucomutase to ensure efficient glucose mobilization. Disruption of AGL halts debranching, leading to phosphorylase-limit dextrin accumulation and impaired glycogen breakdown.
Knockout of AGL in HAP1 cells recapitulates the molecular pathology of glycogen storage disease type III (Cori disease). The near-haploid background ensures complete loss of debranching activity, resulting in cytoplasmic accumulation of abnormal glycogen structures and defective glucose release. This cellular model enables mechanistic dissection of AGL deficiency, analysis of downstream metabolic disturbances, and evaluation of therapeutic strategies such as enzyme replacement or small-molecule chaperones.
AGL Knockout HAP1 Polyclonal Cells support diverse research applications, including drug screening for GSD III, functional validation of AGL mutations, and studies of glycogen metabolism. Compatible assays include Periodic acid-Schiff staining for glycogen, glucose release assays, AGL activity measurements, Western blotting, and RT-qPCR for metabolic genes. This polyclonal population provides a reproducible human model for advancing metabolic disease research and therapeutic development. For technical inquiries, please contact Ascent Research.
