The CD46 Knockout K-562 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the CD46 gene has been disrupted in the human chronic myeloid leukemia cell line K-562. This genetically modified model provides a powerful loss-of-function system for investigating CD46-dependent processes without the limitations of transient knockdown approaches.
The parental K-562 cell line was established from the pleural effusion of a patient in blast crisis of chronic myeloid leukemia and harbors the Philadelphia chromosome (BCR-ABL1 fusion). As a suspension cell line with erythroid and megakaryocytic differentiation potential, K-562 is widely used to study hematopoietic differentiation, leukemia biology, and signal transduction pathways.
CD46, also known as membrane cofactor protein, is a cell-surface glycoprotein that functions as a key regulator of the complement cascade. It acts as a cofactor for the serine protease factor I to cleave and inactivate C3b and C4b deposited on host cells, thereby protecting them from complement-mediated lysis. Beyond complement regulation, CD46 serves as a cellular receptor for measles virus hemagglutinin, adenovirus fiber protein, and Neisseria meningitidis Opa proteins. Ligation of CD46 by natural ligands or pathogens triggers intracellular signaling through its alternatively spliced cytoplasmic tails (Cyt-1 and Cyt-2), activating Src family kinases and downstream pathways including ERK and JNK. Furthermore, CD46 engagement modulates autophagy via ATG5 and LC3 and influences T-cell responses, linking innate immunity with adaptive immune regulation.
In the K-562 context, ablation of CD46 expression creates a model system uniquely suited to examine complement sensitivity in a leukemic background. The knockout cells enable dissection of CD46-mediated protection against complement attack and its role in viral entry, as K-562 cells are permissive to measles and adenovirus infection. Additionally, this model facilitates investigation of CD46’s immunomodulatory functions, such as T-cell modulation and cytokine regulation, providing insights into immune evasion mechanisms in hematopoietic malignancies.
This polyclonal knockout population is ideally configured for a broad range of applications, including complement regulation studies, cancer immunology, viral pathogenesis, and gene therapy vector development. Researchers can employ representative assays such as flow cytometry to verify CD46 ablation, complement-mediated lysis protection assays, western blotting for downstream signaling components (e.g., phospho-Src, LC3), co-immunoprecipitation with C3b, measles virus binding assays, and T-cell modulation assays. For additional information or custom configurations, please contact Ascent Research.
