The IGF1R Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human IGF1R gene in HAP1 cells. This product consists of a heterogeneous mixture of cells with disrupted IGF1R function, enabling the study of loss-of-function phenotypes without clonal selection. It is designed for researchers investigating insulin-like growth factor receptor signaling in a near-haploid human cell background.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML)-derived fibroblast-like cell line. With a stable haploid karyotype, HAP1 cells are widely utilized for haploid genetic screening, functional genomics, and leukemia modeling. Their adherent, fibroblast-like morphology and rapid growth make them well-suited for high-throughput assays and gene perturbation studies.
The IGF1R gene encodes a receptor tyrosine kinase that mediates signaling by insulin-like growth factor 1 (IGF1), IGF2, and insulin. Upon ligand binding, IGF1R autophosphorylates and recruits adaptor proteins IRS1 and SHC, which serve as platforms for activating the PI3K-AKT and RAS-MAPK cascades. Key downstream effectors include mTOR, FOXO1, and ERK1/2, which collectively regulate cell proliferation, survival, and metabolism. The receptor also interacts with GRB2, PI3K p85, beta-arrestin, and integrin beta1, forming a multifaceted signaling network. Disruption of IGF1R blocks these phosphorylation-dependent pathways, abolishing growth factor-driven cellular responses.
In the HAP1 cell context, knockout of IGF1R eliminates a critical mitogenic and survival signal, making this model valuable for dissecting oncogenic mechanisms in CML and other cancers. The near-haploid genome simplifies bi-allelic knockout analysis and facilitates genome-wide synthetic lethal screens and drug sensitivity profiling. Additionally, this model supports studies of insulin resistance and growth retardation, providing a platform to explore IGF1R-related metabolic dysregulation and therapeutic targeting.
Researchers can employ this knockout cell population in a range of assays, including Western blot analysis of phospho-AKT and phospho-ERK to confirm pathway inactivation, RT-qPCR quantification of FOXO1 and FOXO3 transcript levels, and flow cytometry-based cell cycle and apoptosis detection via Annexin V staining. Migration and invasion assays enable functional assessment of IGF1R in cell motility, while drug sensitivity studies test inhibitors such as linsitinib. Co-immunoprecipitation experiments allow interrogation of receptor-adaptor interactions. This product is suited for cancer signaling research, functional genomics, and metabolic pathway analysis. For more information, contact Ascent Research.
