The JAK3 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 143B cell line, featuring targeted disruption of the JAK3 gene. This product is supplied as a heterogeneous pool of edited cells, providing a robust loss-of-function model for studying JAK3-dependent signaling without clonal artifacts. The knockout population maintains the genetic background of the parental 143B line while abrogating JAK3 protein expression, enabling researchers to interrogate cytokine-driven pathways in a malignant bone tumor context. Rigorous quality control ensures the absence of wild-type JAK3 alleles across the population, making it suitable for reproducible functional assays.
The 143B host cell line is a well-characterized model of human osteosarcoma, originally derived from the HOS osteosarcoma line. These adherent, fibroblast-like cells exhibit aggressive tumorigenic properties, including rapid proliferation, invasive capacity, and the ability to form tumors in xenograft models. The 143B line is widely employed in cancer research to investigate mechanisms of bone tumor biology, metastasis, and therapeutic resistance. By introducing a JAK3 knockout into this background, the product offers a unique tool for exploring the non-canonical roles of JAK3 in solid tumors, particularly within the osteosarcoma microenvironment.
JAK3 encodes a cytoplasmic non-receptor tyrosine kinase that selectively associates with the common gamma chain (??c) of cytokine receptors, including receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Upon cytokine binding, JAK3 is activated and phosphorylates specific tyrosine residues on the receptor cytoplasmic tail, creating docking sites for STAT transcription factors such as STAT5, STAT3, and STAT6. JAK3 cooperates with JAK1 to fully transduce signals, leading to STAT dimerization, nuclear translocation, and transcriptional regulation of target genes including BCL2, MYC, and SOCS family members. This signaling cascade is essential for lymphocyte development, proliferation, and differentiation. In the knockout cells, disruption of JAK3 cripples these downstream events, providing a clean system to dissect JAK3??s contributions to gene expression and cellular responses.
Although JAK3 is predominantly associated with hematopoietic lineages, its expression and function in non-immune cells are increasingly recognized. In the osteosarcoma context, JAK3-mediated signals may influence tumor cell survival, proliferative capacity, and interactions with the bone marrow niche. By eliminating JAK3 in 143B cells, researchers can directly assess how its loss impacts oncogenic phenotypes, such as anchorage-independent growth and resistance to apoptosis, potentially mediated through altered STAT activation and expression of pro-survival factors like BCL2. This model is particularly valuable for evaluating the therapeutic relevance of JAK3 inhibition in bone cancers and for delineating crosstalk between JAK3-dependent pathways and other oncogenic drivers.
This product enables a wide range of experimental applications, including western blotting for JAK3 and phospho-STATs to confirm knockout efficiency and signaling impairment, and RT-qPCR for SOCS3 to quantify transcriptional effects. Cytokine stimulation assays with IL-2, IL-4, or IL-15 can be employed to test residual signaling competence. Functional phenotypic analyses include cell proliferation assays using MTS, apoptosis detection by Annexin V staining, and migration/invasion Boyden chamber assays to evaluate the impact of JAK3 loss on metastatic behavior. Moreover, these cells serve as a platform for drug sensitivity screening against JAK inhibitors or for functional genomics screens to identify synthetic lethal partners. For further information or support, please contact Ascent Research.
