The DUSP21 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HAP1 human near-haploid myeloid leukemia cell line. This product contains a heterogeneous pool of cells with targeted disruptions of the DUSP21 gene, which encodes a dual-specificity phosphatase. The polyclonal knockout format minimizes clonal artifacts and provides a genetically diverse background for investigating DUSP21-mediated negative regulation of stress-activated MAP kinase pathways.
HAP1 is a near-haploid human myeloid leukemia line derived from KBM-7 chronic myeloid leukemia blast crisis cells. Its near-haploid karyotype, with a single disomic region on chromosome 15, allows unambiguous genetic analysis, making it ideal for knockout studies. As a myeloid-derived cell line, HAP1 responds to inflammatory stimuli such as TNF, IL-1, and TLR ligands, providing a relevant model for innate immune signaling and myeloid cell biology.
DUSP21 is a dual-specificity phosphatase that inactivates JNK and p38 MAP kinases, thereby attenuating stress-activated MAPK signaling. Its expression is induced by inflammatory stimuli including TNF, IL-1, and TLR ligands such as LPS. DUSP21 directly interacts with JNK1, JNK2, and p38 MAPK, as well as upstream activating kinases MKK3, MKK6, MKK4, and MKK7. Key downstream transcription factors regulated by this pathway are c-Jun and ATF2, which control pro-inflammatory cytokine expression. Representative upstream kinases ASK1 and TAK1 activate the cascade upon cellular stress or immune receptor engagement.
In the HAP1 myeloid background, DUSP21 knockout is expected to enhance and prolong JNK and p38 activation upon inflammatory stimulation, leading to increased cytokine production. This model is particularly valuable for studying the dysregulated MAPK signaling underlying inflammatory and autoimmune diseases such as rheumatoid arthritis. The near-haploid genome simplifies genetic interaction screens, enabling the identification of modulators that synergize with or compensate for DUSP21 loss.
These DUSP21 knockout cells are ideal for genetic screens to identify MAPK pathway regulators or synthetic lethal interactions. They enable quantitative analysis of JNK and p38 phosphorylation via western blotting or phospho-flow cytometry after treatment with TNF, IL-1, or LPS. Cytokine secretion can be measured by ELISA, and transcriptional responses assessed through RT-qPCR or AP-1 luciferase reporter assays. Co-immunoprecipitation experiments can validate physical interactions between DUSP21 and its MAPK substrates. Additionally, the cells serve as a platform for drug target validation in inflammatory disease research. For further information, please contact Ascent Research.
