The GPNMB Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the HAP1 human chronic myeloid leukemia cell line, designed for loss-of-function studies of the GPNMB gene. This product provides a versatile genetic background for investigating the roles of GPNMB in cell adhesion, migration, differentiation, and signaling. The polyclonal format ensures representation of multiple knockout alleles, facilitating robust phenotypic analyses without the need for clonal isolation.
HAP1 cells are a near-haploid, adherent human male cell line derived from the KBM-7 chronic myeloid leukemia line, harboring the BCR-ABL fusion gene.
Their haploid karyotype and stable genetic background make them an ideal model for gene targeting and CRISPR-based knockout screens, enabling efficient generation and study of gene disruptions. This host cell line is widely used in pathway analysis, drug target validation, and genome-wide screening due to its ease of manipulation and consistent growth characteristics.
GPNMB is a type I transmembrane glycoprotein that functions as both an adhesion molecule and a signaling receptor. Its intracellular domain recruits FAK and Src kinases upon ECM engagement or CD44 binding, leading to ERK1/2 and Akt phosphorylation and thus promoting migration, invasion, and survival.
Ectodomain shedding by ADAM10 releases a soluble fragment with paracrine activity. Transcription of GPNMB is driven by MITF, TGF-??, TNF-??, and HIF-1??. Downstream, GPNMB activates FAK/Src?CERK, PI3K/Akt, and NF-??B pathways, inducing MMP-3, MMP-9, cathepsin K, and TRAP.
It interacts with integrins ??5??1 and ??v??3, syndecan-4, HSPG, LRP1, and SPARC to integrate adhesion and growth factor signals.
In the HAP1 background, GPNMB knockout eliminates its contribution to adhesion-mediated signaling, making this polyclonal population a powerful tool for dissecting the gene??s function in a simplified, haploid genomic context. Loss of GPNMB is expected to attenuate FAK/Src-dependent pathway activation, impair integrin-mediated adhesion, and reduce downstream effector responses. This model is particularly suited for studying the molecular mechanisms by which GPNMB supports aggressive phenotypes in cancers and inflammatory diseases, as well as for evaluating compensatory signaling networks that may emerge upon its loss.
These knockout cells are ideally suited for a range of experimental applications, including cancer metastasis studies, osteoclast differentiation research, fibrosis modeling, and drug target validation.
They enable the use of assays such as Western blotting for phospho-ERK and phospho-Akt, RT-qPCR for MMP and cathepsin expression, cell migration and invasion assays, adhesion to ECM substrates, flow cytometry for surface GPNMB, and co-immunoprecipitation with CD44 or integrins. In osteoclast biology, TRAP staining and cathepsin K measurement can be employed. Additionally, the cells may serve as a control for GPNMB-targeted immunotherapies and biomarker discovery. For further details, please contact Ascent Research.
