The HRH1 knockout HAP1 polyclonal cells are a CRISPR/Cas9-edited polyclonal knockout cell population engineered for loss-of-function studies of the human HRH1 gene. This gene-targeted disruption model lacks functional histamine H1 receptor expression, enabling researchers to investigate HRH1-dependent signaling, allergy and inflammation pathways, and antihistamine pharmacology. The polyclonal knockout format provides a heterogeneous population of HRH1-disrupted HAP1 cells, avoiding the artifacts associated with single-cell cloning while retaining the near-haploid karyotype advantages for functional genomics.
HAP1 is a near-haploid human myeloid leukemia cell line derived from the KBM-7 chronic myeloid leukemia (CML) line, carrying the BCR-ABL1 fusion oncogene. Due to its haploid chromosome set, HAP1 is a widely used model for genetic screening, CRISPR-based knockout studies, and functional validation of signaling pathways. Its adherent growth and stable near-haploid state simplify genome editing and phenotypic analysis, making it an ideal host for generating knockout cell populations such as this HRH1-disrupted HAP1 model.
HRH1 encodes the histamine H1 receptor, a Gq/11-coupled GPCR that mediates major histamine-induced cellular responses. Upon ligand binding, the activated receptor interacts with Gq/11 proteins to stimulate phospholipase C ?? (PLC??), generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium ion release from intracellular stores, while DAG activates protein kinase C (PKC). These second messengers drive downstream signaling cascades, including NF-??B and MAP kinase (ERK1/2) pathways, ultimately regulating pro-inflammatory gene expression. ??-arrestins and G protein-coupled receptor kinases modulate receptor desensitization and internalization. Disruption of HRH1 ablates this signaling axis, providing a clean background to dissect histamine-dependent events.
In the HAP1 cellular context, HRH1 knockout eliminates histamine-triggered calcium mobilization and downstream kinase activation, enabling precise dissection of H1 receptor-mediated biology without interference from endogenous receptor activity. The near-haploid background ensures that loss-of-function effects are unambiguous, as there is no second allele to compensate. This model is particularly suited for studying allergic inflammation mechanisms, screening potential H1 receptor inverse agonists or antagonists, and identifying signaling adaptors involved in GPCR trafficking. The polyclonal nature of the knockout population reflects the diversity of editing events, which can be used to assess on-target consistency across multiple mutation variants.
Typical applications include calcium flux assays to measure H1 receptor function, NF-??B or NFAT reporter gene assays for transcriptional responses, western blotting for phospho-PLC?? or phospho-ERK to assess signaling, IP3 accumulation assays, and RT-qPCR analysis of histamine-induced pro-inflammatory cytokines. The cells are also useful for flow cytometry-based receptor expression profiling and histamine-induced cytokine secretion assays. This knockout model supports allergy and inflammation research, GPCR signal transduction studies, antihistamine drug screening, and immunological functional genomics. For further technical information or to request a quotation, contact Ascent Research.
