The IL17RA Knockout HAP1 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population in which IL17RA gene disruption generates a loss-of-function model for interleukin-17 receptor A signaling. Derived from the near-haploid HAP1 line, this polyclonal knockout pool is designed for functional genomics, pathway analysis, and drug discovery, providing a robust, population-level tool for interrogating IL-17-dependent processes without clonal selection biases.
HAP1 is a fibroblast-like, chronic myelogenous leukemia-derived near-haploid human cell line originating from KBM-7. Its near-haploid karyotype simplifies genetic manipulation, permitting efficient single-allele targeting and unambiguous phenotype interpretation. HAP1 supports high-throughput haploid screens and offers rapid proliferation along with intact cytoplasmic signaling machinery, making it ideal for studying pathways relevant to leukemia and inflammation.
IL17RA encodes a receptor subunit for IL-17A and IL-17F, functioning as an obligate component of the IL-17 receptor complex. Ligand binding induces heterodimerization with IL17RC, recruitment of adaptor TRAF3IP2 (Act1) and E3 ligase TRAF6, and activation of TAK1 (MAP3K7). This stimulates the IKK complex (IKBKB, IKBKG, CHUK) to drive NF-??B (p65/p50) nuclear translocation, while also triggering MAPK cascades (JNK, ERK, p38) and AP-1. Downstream, transcription of pro-inflammatory mediators such as IL-6, TNF-??, CXCL8, CCL2, and MMP9 is induced. IL17RA knockout abrogates receptor complex formation, preventing Act1-TRAF6-dependent signal propagation and blocking cytokine production.
Coupling IL17RA knockout with the HAP1 near-haploid background establishes a simplified, sensitive system for dissecting IL-17 receptor biology. The polyclonal disruption ensures functional inactivation at the population level, while the haploid state eliminates diploid compensatory effects. This model is valuable for examining how IL17RA-driven inflammation intersects with leukemia-related signaling and for performing synthetic lethality or drug combination screens. It enables clean assessment of IL-17 pathway dependencies without confounding receptor activity.
Researchers can utilize these cells for phospho-p65 and phospho-JNK western blotting, IL-6/CXCL8 RT-qPCR, ELISA-based cytokine measurement, NF-??B luciferase assays, ChIP, and p65 immunofluorescence. Additional applications include flow cytometric confirmation of surface IL17RA loss, co-IP analysis of receptor complex disruption, and high-throughput haploid genetic screening. The model supports drug target validation for autoimmune diseases (e.g., psoriasis, rheumatoid arthritis) and identification of novel IL-17 pathway regulators via phospho-signaling arrays. For further information, please contact Ascent Research.
