The IFNAR2 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human HAP1 cell line. This pool contains cells with diverse disruptions in the IFNAR2 gene, creating a loss-of-function model for type I interferon (IFN) signaling studies. The polyclonal format enables pooled screening and functional genomics applications without clonal selection bias.
HAP1 is a chronic myelogenous leukemia-derived cell line with a near-haploid karyotype, isolated from a male patient. Its haploidy allows single-allele disruption to yield a functional knockout, making it ideal for genetic screens and CRISPR-based mutagenesis. These adherent cells proliferate rapidly and offer a simplified genetic landscape, reducing redundancy in signaling pathway analysis. The IFNAR2 knockout in HAP1 provides a clean background for dissecting type I IFN responses.
IFNAR2 encodes the beta subunit of the type I IFN receptor, which pairs with IFNAR1 to bind IFN-??/??. Ligand binding activates TYK2 and JAK1, leading to phosphorylation of STAT1 and STAT2. These associate with IRF9 to form the ISGF3 complex, which transcriptionally activates ISGs such as ISG15, OAS1, and MX1. This JAK-STAT cascade drives antiviral, antiproliferative, and immunomodulatory programs. Knockout of IFNAR2 ablates receptor-kinase coupling, preventing STAT activation and downstream ISG induction, thus compromising innate antiviral defenses.
In HAP1 cells, the polyclonal IFNAR2 knockout population facilitates interrogation of type I IFN signaling with minimal genetic complexity. Haploidy ensures complete protein loss per edited cell, yielding a defined phenotype. This model is valuable for host-pathogen interaction studies, including viral infection susceptibility, and for modeling IFNAR2-related immunodeficiency 44 or autoimmune conditions. The population format also supports unbiased genetic modifier screens for IFN responsiveness and drug target identification.
Typical applications include monitoring STAT1/STAT2 phosphorylation by western blot, quantifying interferon-stimulated gene (ISG) induction via RT-qPCR (e.g., ISG15, OAS1, MX1), performing interferon bioassays, evaluating viral replication kinetics, and profiling surface receptor expression by flow cytometry. These cells support drug screening campaigns targeting the JAK-STAT pathway and are instrumental for validating gene-editing phenotypes in functional genomics studies. For additional technical details, please contact Ascent Research.
