The JAK2 Knockout 143B Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population in which the JAK2 gene has been disrupted in the human osteosarcoma cell line 143B. This polyclonal knockout model provides a mixed population of cells carrying diverse editing events, enabling loss-of-function studies of JAK2 without clonal selection. The knockout was generated via CRISPR/Cas9-mediated target-gene disruption, resulting in a heterogeneous pool suitable for functional genomics, drug response profiling, and pathway interrogation in a malignant bone tumor background.
The host 143B cell line is a well-characterized osteosarcoma model derived from a 13-year-old female patient and represents a subclone of the TE85 line. 143B cells are widely employed as a model for malignant bone tumors and osteoblastic differentiation, offering a relevant system to study tumorigenesis and bone biology. Their osteosarcoma origin provides a platform to investigate how JAK2-dependent signaling influences cancer cell behavior in the context of a solid tumor, complementing its well-established roles in hematological malignancies.
JAK2 encodes a non-receptor tyrosine kinase that associates with the cytoplasmic domains of cytokine receptors, including the erythropoietin receptor (EPOR), thrombopoietin receptor (MPL), and interleukin receptors such as IL-3R, IL-5R, and IL-6R. Upon ligand binding, JAK2 undergoes transphosphorylation and subsequently phosphorylates downstream STAT transcription factors (STAT3, STAT5, STAT1), leading to their nuclear translocation and transcriptional activation of target genes. Additionally, JAK2 activates the PI3K-AKT-mTOR and MAPK-ERK1/2 cascades, promoting expression of pro-survival and proliferative factors like BCL-XL, c-MYC, and PIM1. Negative regulation is mediated by SOCS1, SOCS3, and SHP1, which feedback to attenuate signaling.
In the 143B osteosarcoma model, JAK2 disruption permits dissection of cytokine-driven signaling pathways in a solid tumor environment that may exhibit aberrant JAK-STAT activity. By eliminating JAK2 function, researchers can investigate its contribution to osteosarcoma cell proliferation, differentiation, and survival, and evaluate how compensatory pathways sustain growth. This polyclonal knockout population is particularly valuable for studying heterogeneity in pathway dependency and for assessing the effects of JAK2 loss in a bone cancer milieu, offering insights that may extend to other solid tumors with activated cytokine signaling.
This product supports a broad array of experimental applications, including western blot analysis of phosphorylated JAK2 and STATs, RT-qPCR profiling of STAT target gene expression, cell proliferation assays (MTT/BrdU), and flow cytometric detection of phospho-STAT5. It is well-suited for drug sensitivity screening with JAK2 inhibitors such as ruxolitinib, co-immunoprecipitation studies of JAK2-receptor interactions, and functional assessment in bone cancer research. The polyclonal nature enables robust population-level analyses while mimicking the heterogeneity of tumor cell pools. For comprehensive product specifications and ordering information, please contact Ascent Research.
