This product consists of a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HAP1 cell line, engineered to disrupt the IL1RAP gene. IL1RAP (interleukin-1 receptor accessory protein) serves as an essential co-receptor for the IL-1, IL-33, and IL-36 receptor families. The polyclonal nature of this knockout pool ensures a heterogeneous mix of loss-of-function alleles across the population, making it particularly suitable for pooled functional screens and bulk biochemical assays. CRISPR/Cas9-mediated gene disruption abrogates IL1RAP expression, enabling dissection of its role in cytokine signaling without the need for single-cell cloning.
The HAP1 host cell line is a near-haploid human chronic myeloid leukemia (CML) cell line that grows in suspension. This haploid karyotype simplifies genetic analysis by eliminating the complexity of diploid gene redundancy, making HAP1 cells an invaluable tool for functional genomics and mutagenesis screens. As a CML-derived model, HAP1 retains features of leukemic signaling and proliferation, providing a relevant context for studying oncogenic pathways and cytokine networks within the hematopoietic lineage.
IL1RAP functions as a shared co-receptor that forms signaling complexes with the ligand-binding receptors IL1R1, ST2 (IL1RL1), and IL1RL2 upon engagement of their respective cytokines IL-1??/??, IL-33, and IL-36. These interactions recruit the adaptor protein MyD88 and kinases IRAK1 and IRAK4, leading to activation of TRAF6 and downstream TAK1. This cascade culminates in the phosphorylation and nuclear translocation of NF-??B and activation of MAP kinases p38 and JNK, driving the transcription of pro-inflammatory mediators such as IL-6, TNF-??, IL-8, CXCL1, and CCL2. Disruption of IL1RAP thus blocks signal transduction from multiple IL-1 family cytokines, providing a potent tool to interrogate convergent inflammatory pathways.
In the HAP1 CML background, loss of IL1RAP offers a unique model to explore autocrine and paracrine cytokine loops that may sustain leukemic cell survival and proliferation. Haploid genetics combined with IL1RAP knockout enables high-throughput identification of synthetic lethal interactions and resistance mechanisms relevant to CML and acute myeloid leukemia (AML). Additionally, the model facilitates investigation of IL-1 family-driven inflammatory responses in a human myeloid context, bridging innate immunity and hematologic malignancy.
This polyclonal IL1RAP knockout cell pool is suitable for a broad range of applications, including cytokine stimulation assays coupled with phospho-signaling analysis (e.g., p-NF-??B, p-p38), ELISA quantification of secreted IL-6 and IL-8, NF-??B luciferase reporter assays, and co-immunoprecipitation to study receptor complex assembly. It is also well-suited for drug sensitivity studies targeting IL-1 pathways and for genome-wide CRISPR screens to uncover novel modulators of inflammatory signaling. For technical inquiries or ordering information, please contact Ascent Research.
