The IGF2R Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the insulin-like growth factor 2 receptor (IGF2R) gene. This loss-of-function model uses the HAP1 near-haploid human cell background to enable studies of IGF2R-dependent processes. The polyclonal format provides a range of knockout alleles without clonal selection bias.
HAP1 cells are a human near-haploid chronic myeloid leukemia line derived from BCR-ABL-positive KBM-7 cells. They are haploid for most chromosomes except chromosome 8 and a segment of chromosome 15, and they are deficient in p53 tumor suppressor function. This unique genetic architecture simplifies functional genetics and is widely employed for genetic screens and mechanistic studies in cancer research.
IGF2R functions as a clearance receptor for insulin-like growth factor II (IGF-II), binding extracellular IGF-II and mediating its endocytosis and lysosomal degradation. By sequestering IGF-II, the receptor suppresses activation of IGF1R and insulin receptor (INSR) signaling, leading to decreased phosphorylation of AKT and ERK kinases. Additionally, IGF2R transports mannose-6-phosphate (M6P)-tagged lysosomal hydrolases from the trans-Golgi network to lysosomes, a critical step for lysosomal enzyme maturation and function. The receptor interacts with clathrin adaptors GGA1, GGA2, and GGA3, the retromer complex, and participates in TGF-beta latent complex activation. Transcriptional regulation of IGF2R is mediated by TP53, linking its expression to tumor suppressive pathways.
Disruption of IGF2R in the p53-null HAP1 background provides a potent model to explore the convergence of tumor suppression and mitogenic signaling. The absence of p53 highlights IGF2R’s role in limiting IGF1R/INSR pathway activity, potentially unmasking oncogenic effects upon receptor loss. The haploid genome ensures that knockout phenotypes are unambiguous, facilitating clear interpretation of gene function in proliferation and lysosomal trafficking studies. This context is particularly valuable for investigating mechanisms of growth factor-dependent oncogenesis.
These polyclonal knockout cells are suitable for Western blot analysis of IGF2R and phosphorylated AKT, ELISA-based quantification of IGF-II, ligand internalization assays, and lysosomal enzyme activity measurements. They support applications in cancer biology, drug target validation, and lysosomal storage disorder research. Co-immunoprecipitation can assess interactions with GGA adaptors or retromer components, while proliferation and apoptosis assays examine cellular consequences of IGF2R loss. For further information, please contact Ascent Research.
