KYAT1 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the KYAT1 gene in near-haploid human HAP1 cells. This product consists of a heterogeneous pool of cells with gene disruptions, offering a robust loss-of-function model for investigating kynurenine aminotransferase 1 function without clonal isolation. The polyclonal format is ideal for large-scale genetic screens and preliminary functional studies.
Derived from a human chronic myeloid leukemia (CML) patient, HAP1 cells are adherent, fibroblast-like, and near-haploid. Their single-copy chromosome status simplifies genetic engineering and ensures unambiguous knockout phenotypes, making them a favored platform for functional genomics and pathway analysis. HAP1 cells are particularly effective for studying genes involved in metabolism and signal transduction.
KYAT1 encodes a pyridoxal phosphate (PLP)-dependent homodimeric enzyme that transaminates kynurenine to kynurenic acid, a crucial metabolite in the kynurenine pathway. Kynurenic acid acts as an endogenous NMDA receptor antagonist and negative allosteric modulator of alpha7 nicotinic acetylcholine receptors, regulating glutamatergic and cholinergic signaling. Its expression is induced by pro-inflammatory cytokines (IL-1??, TNF-??, IFN-??) and glucocorticoids. Upstream pathway components include IDO and TDO, which generate kynurenine, while downstream 3-hydroxykynurenine and quinolinic acid contribute to neuroactive balance. In addition to its transaminase activity, KYAT1 possesses cysteine conjugate beta-lyase activity, expanding its metabolic roles. KYAT1 knockout therefore abolishes kynurenic acid synthesis, removing its neuromodulatory actions.
In the HAP1 background, KYAT1 disruption eliminates kynurenic acid production, creating a clean system to examine its impact on receptor antagonism and excitotoxicity. This model is highly relevant for neurological disease research, including schizophrenia, Alzheimer’s disease, and bipolar disorder, where kynurenine pathway dysregulation is implicated. The near-haploid nature ensures efficient knockout, minimizing residual activity, and provides a defined genetic context for reproducible results.
Applications include validation via western blotting, RT-qPCR, and Sanger sequencing; metabolic profiling by LC-MS-based kynurenic acid quantification; and functional assays such as NMDA receptor antagonist activity and glutamate release measurements. The model supports neurobiology, neuroinflammation, excitotoxicity, and drug metabolism studies, enabling dissection of cytokine-mediated pathway control. For further technical details and ordering information, please contact Ascent Research.
