The CCL11 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population providing a heterogeneous pool with targeted disruptions in the CCL11 gene. This product is ideal for pooled functional genomics and bulk assays, enabling loss-of-function studies of eotaxin-1, a chemokine critical for eosinophil recruitment and allergic inflammation.
HAP1 is a near-haploid human cell line derived from the KBM-7 CML line, which carries the BCR-ABL fusion. Its haploid genome simplifies gene editing and phenotypic analysis, as single-allele targeting yields functional knockout without compensatory effects. This background is valuable for studying signaling pathways in both leukemic and normal hematopoietic contexts.
CCL11 encodes eotaxin-1, a chemokine that selectively activates the CCR3 receptor on eosinophils, triggering G??i-mediated signaling. This cascade engages GNAI proteins, PLCB, and IP3, leading to calcium flux and activation of PI3K-AKT and MAPK/ERK pathways, resulting in phosphorylation of MAPK1/3 (ERK) and AKT1, and RAC1-driven actin polymerization for chemotaxis and degranulation. Transcriptionally, CCL11 is induced by IL-4 and IL-13 via STAT6, and by TNF-?? via NF-??B, with additional regulation by TSLP and IL-33. It also interacts with DARC and ??-arrestins.
In HAP1 cells, knockout of CCL11 eliminates endogenous eotaxin-1, disrupting CCR3-dependent signaling modules such as calcium flux and ERK phosphorylation. While HAP1 lacks endogenous eosinophil machinery, paracrine reconstitution or co-culture models enable dissection of eosinophil chemotaxis. The haploid background also supports synthetic lethality screens to identify modifiers of CCL11 pathway dependency.
Research applications include mechanistic studies of eosinophilic asthma, atopic dermatitis, and chemokine receptor pharmacology. Typical assays involve RT-qPCR, ELISA, and western blot for pathway markers, along with CCR3-mediated calcium flux and transwell chemotaxis assays. Genome-wide screens and RNA-seq can uncover global effects of CCL11 loss. For more information, contact Ascent Research.
