The DUSP10 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population featuring targeted disruption of the DUSP10 gene (encoding MKP5). Supplied as a heterogeneous pool, this loss-of-function model retains functional diversity for pooled screening and population-level analyses within a near-haploid genetic background.
Hosted by HAP1 cells??a near-haploid, suspension-adapted line derived from KBM-7 chronic myeloid leukemia (CML) cells in blast crisis??this male-origin line is extensively used in genetic screening and functional genomics. Its ease of genetic manipulation and ability to achieve gene disruption via single-allele editing make it ideal for CRISPR-based studies. HAP1 retains CML-relevant signaling features, providing a pertinent model for kinase-dependent cancer and inflammation research.
DUSP10 (MKP5) is a dual-specificity phosphatase that selectively dephosphorylates and inactivates the stress-activated MAP kinases p38 and JNK. Its expression is induced by pro-inflammatory cytokines such as TNF-?? and IL-1, acting downstream of TNFR/TLR receptor complexes and upstream MAP3Ks like ASK1. Within the signaling cascade, DUSP10 directly interacts with p38??, JNK1, and JNK2, often in complex with JIP scaffold proteins, to dephosphorylate these kinases. This action suppresses downstream effectors including the AP-1 transcription factor complex (c-Jun/c-Fos), ATF2, and the production of cytokines IL-6 and TNF-??. Consequently, DUSP10 functions as an inducible feedback inhibitor that restrains MAPK-mediated inflammatory and stress responses.
In the HAP1 environment, disruption of DUSP10 relieves this negative regulatory loop, resulting in sustained or amplified p38 and JNK activation upon stimulation. This polyclonal knockout model thus offers a powerful system to dissect how loss of DUSP10 alters MAPK pathway output in a CML-derived background, bridging oncogenic and inflammatory signaling. The near-haploid genome facilitates clear genotype?Cphenotype associations, enabling efficient genetic modifier screens and drug?Cgene interaction studies in a homogeneous cellular context.
Representative applications include phospho-p38 and phospho-JNK immunoblotting, AP-1 luciferase reporter assays, ELISA quantification of IL-6 and TNF-??, and flow cytometric analysis of phosphorylated MAPKs. Cell proliferation under oxidative or cytokine stress and drug sensitivity screening for modulators of DUSP10-dependent pathways are readily performed. This model supports studies of MAPK signaling dynamics, functional genomics screens, and investigation of DUSP10??s roles in inflammatory disorders and cancer drug resistance. For further information, contact Ascent Research.
