The IL1R1 Knockout HAP1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the IL1R1 gene, which encodes the interleukin-1 receptor type 1. This heterogeneous pool of HAP1 cells carries targeted gene disruptions introduced by CRISPR/Cas9-mediated genome editing, providing a loss-of-function model for investigating IL-1 signaling without the need for clonal isolation. The polyclonal format captures a range of editing events, enabling robust functional studies while preserving the inherent biological variability of a near-haploid genetic background.
HAP1 cells are a near-haploid human cell line derived from a male patient with chronic myeloid leukemia, originally isolated from the KBM-7 cell line. These cells maintain a haploid karyotype except for disomy of chromosome 15, making them an exemplary model for functional genomics and genetic screens. The simplified genome reduces genetic redundancy, allowing unambiguous genotype-phenotype correlations, which is particularly advantageous for exploring signal transduction pathways that might be masked in diploid cells.
IL1R1 is a critical receptor in the innate immune system, binding the pro-inflammatory cytokines IL-1?? and IL-1?? to initiate intracellular signaling cascades. Upon ligand engagement, IL1R1 recruits the accessory protein IL1RAP and the adaptor MyD88, leading to the sequential activation of IRAK4 and IRAK1 kinases. This assembly promotes TRAF6-mediated ubiquitination events that activate TAK1, resulting in the phosphorylation of IKK complex and subsequent NF-??B translocation, as well as the stimulation of MAPK pathways involving JNK, p38, and ERK1/2. Downstream transcriptional responses include the upregulation of pro-inflammatory mediators such as IL6, IL8, TNF, and PTGS2, which are central to inflammatory disease pathogenesis.
In the HAP1 cellular context, disruption of IL1R1 provides a clean genetic system to dissect IL-1 signal transduction. The near-haploid background simplifies the interpretation of knockout phenotypes by eliminating confounding gene copies, enabling researchers to directly assess the requirement of IL1R1 for cytokine responsiveness. This model is particularly valuable for examining how IL1R1 couples to downstream effectors such as NF-??B and MAPK modules, and for evaluating the roles of interacting regulators like IL1RN, TOLLIP, and SIGIRR without interference from wild-type alleles.
This knockout cell pool is an essential tool for a range of biomedical research applications, including inflammatory disease modeling, high-throughput screening for IL-1 pathway inhibitors, and functional genomics studies. Researchers can employ representative assays such as Western blotting for phospho-signaling analysis, RT-qPCR and RNA-seq for transcriptional profiling, ELISA for cytokine secretion measurement, NF-??B reporter assays for pathway activity, and flow cytometry for receptor expression. The model is well-suited for investigating autoinflammatory disorders, rheumatoid arthritis, and sepsis, and for screening therapeutic candidates targeting IL-1 signaling. For technical inquiries and ordering information, please contact Ascent Research.
