The MS4A6A Knockout THP-1 Cell Line is a CRISPR/Cas9-edited human monocytic cell line engineered for loss-of-function studies of the MS4A6A gene. This gene-edited product enables researchers to dissect the role of MS4A6A in immune signaling and cellular processes without altering the broader genomic context of the THP-1 parental line. Through targeted disruption of the MS4A6A locus, this model provides a stable, genetically defined platform for functional genomics, drug screening, and mechanistic investigations.
THP-1 cells are derived from the peripheral blood of a one-year-old male with acute monocytic leukemia (AML-M5) and are widely employed as a model for monocyte/macrophage biology. Upon stimulation with agents such as phorbol 12-myristate 13-acetate (PMA), THP-1 cells differentiate into macrophage-like cells, enabling studies of adhesion, phagocytosis, and cytokine production. The cell line retains key signaling pathways relevant to innate immunity, including NF-??B, Toll-like receptor (TLR), and calcium-dependent cascades, making it a versatile host for gene editing applications.
MS4A6A encodes a member of the membrane-spanning 4A (MS4A) family of transmembrane proteins that modulate ion fluxes and immune receptor signaling. It regulates intracellular calcium levels through interactions with calmodulin and MS4A4A. The protein operates downstream of immune receptors such as Fc??RI and TLR4, influencing effectors including SYK, PLC??2, and DAP12. Its expression is induced by transcription factors NF-??B, AP-1, and PU.1 in response to LPS and IFN-??. MS4A6A then modulates calcium flux, NFAT activation, and production of TNF-?? and IL-6, while also regulating phagocytosis and ROS generation.
In THP-1 cells, MS4A6A knockout disrupts inflammatory responses and phagocytosis, key functions for studying neuroinflammation. The model is valuable for the TREM2-DAP12 pathway linked to Alzheimer’s disease risk. Loss of MS4A6A attenuates calcium-dependent cascades and dampens NF-??B and MAPK signaling, providing a controlled system to dissect immune dysregulation. This line bridges basic immunology and translational research in AML and neurodegeneration.
Researchers can apply this knockout cell line in functional studies. RT-qPCR and Western blotting verify MS4A6A disruption, while flow cytometry profiles surface markers. Calcium flux assays, phagocytosis assays, and cytokine ELISA quantify immune responses. NF-??B reporter assays monitor signaling activity, and co-immunoprecipitation examines interactions with calmodulin or DAP12. This model supports monocyte function studies, Alzheimer’s-related microglial signaling investigations, and drug screening for neuroinflammatory and leukemic conditions. Contact Ascent Research for more information.
