The GPR75 Knockout 143B Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population originating from the 143B human osteosarcoma cell line, designed for targeted disruption of the GPR75 gene. This heterogeneous pool of edited cells serves as a loss-of-function model for interrogating GPR75 function without clonal selection bias. The gene disruption impairs GPR75-mediated signaling, allowing dissection of its role in cellular physiology.
The 143B cell line is a well-established model of human osteosarcoma, characterized by a mutant TP53 tumor suppressor. Known for its aggressive growth and invasive capacity, 143B serves as a relevant host for studying cancer-related pathways and therapeutic targets. The osteosarcoma background, combined with p53 deficiency, makes this knockout system particularly useful for exploring the intersection of GPCR signaling and tumor metabolism.
GPR75 encodes a chemerin (RARRES2)-responsive G protein-coupled receptor that couples to G??i/o and G??q/11 proteins. Ligand engagement triggers intracellular cAMP modulation and calcium mobilization, while also promoting ??-arrestin-2 recruitment. These events activate downstream MAPK/ERK and PI3K-AKT cascades, ultimately regulating NF-??B-mediated transcription. Consequently, GPR75 links adipokine signals to key pathways??including cAMP, MAPK, and adipocytokine signaling??controlling metabolic and inflammatory responses.
In 143B osteosarcoma cells, knockout of GPR75 disrupts chemerin-dependent signaling, leading to attenuated cAMP and calcium fluxes. This impairment results in reduced MAPK/ERK and PI3K-AKT activation, affecting cell proliferation, survival, and metabolic reprogramming. Thus, the model enables dissection of how GPCR-mediated signals influence cancer cell behavior, particularly in a p53-mutant background, and provides insight into the role of chemerin in tumor progression and metabolism.
These polyclonal knockout cells are applicable in obesity research, metabolic disease modeling, and GPCR signal transduction studies. They support drug target validation for metabolic disorders and osteosarcoma, enabling assays such as western blotting, RT-qPCR, cAMP measurement, calcium flux analysis, and phospho-ERK/AKT detection. Further functional analyses, including proliferation, migration, and RNA-seq, facilitate comprehensive pathway characterization. For additional technical details, please contact Ascent Research.
