The JAM3 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human liver sinusoidal endothelial cell line SK-HEP-1, engineered for loss-of-function studies of junctional adhesion molecule 3 (JAM3). This product provides a heterogeneous cell population with targeted disruption of JAM3, enabling investigation of endothelial barrier function, leukocyte transmigration, and angiogenesis without clonal artifacts. The polyclonal format retains inherent genetic diversity of the parental line, offering a robust and reproducible model for population-level functional assays.
SK-HEP-1 cells serve as a well-characterized model of human liver sinusoidal endothelial cells (LSECs), performing filtration, receptor-mediated endocytosis, and immune surveillance functions. They express endothelial markers including VE-cadherin and CD31, and maintain the capacity for dynamic junctional remodeling, cytokine responsiveness, and bidirectional interaction with circulating leukocytes and metastatic tumor cells. This cell line recapitulates key facets of the hepatic sinusoidal microenvironment, making it a physiologically relevant host for JAM3 knockout studies.
JAM3 is a tight junction transmembrane adhesion molecule that forms cis-homodimers and heterodimers with JAM2, recruiting scaffold proteins ZO-1, cingulin, and afadin to anchor junctions to the perijunctional actin cytoskeleton. It also binds leukocyte integrin ??M??2 (Mac-1), triggering endothelial signaling cascades that facilitate diapedesis. JAM3 expression is regulated by VEGF, TNF-??, IL-1??, and Wnt/??-catenin pathways, while downstream it activates RhoA/ROCK and Rac1 GTPases, actin remodeling, and JNK signaling. Disruption of JAM3 abrogates critical protein?Cprotein interactions, leading to compromised barrier integrity and impaired transendothelial migration.
In the liver sinusoidal context, JAM3 knockout provides a powerful platform to dissect tight junction contributions to vascular permeability and immune cell trafficking. This model is directly relevant to diseases such as hemorrhagic destruction of the brain with subependymal calcifications and cataracts (HDBSCC), where JAM3 mutations cause severe vascular defects, as well as cancer metastasis and inflammatory vascular disorders. The LSEC background allows investigation of how JAM3 loss alters liver-specific endothelial functions, including filtration dynamics and metastatic cell extravasation.
Research applications include transendothelial electrical resistance (TEER) and tracer permeability assays, Transwell leukocyte migration and cancer cell extravasation studies, tube formation angiogenesis assays, and co-immunoprecipitation or immunofluorescence analysis of tight junction complexes. Flow cytometry, Western blotting, and RT-qPCR enable quantification of downstream effectors such as RhoA, Rac1, and JNK. These cells are also suitable for drug screening targeting vascular integrity or anti-metastatic compounds. For further product details or technical assistance, please contact Ascent Research.
