DTNBP1 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for functional studies of the DTNBP1 gene. This product comprises a heterogeneous pool of NCI-H1299 cells harboring CRISPR/Cas9-mediated disruptions of DTNBP1, ensuring robust loss-of-function phenotypes without clonal selection.
The parental NCI-H1299 cell line is a human epithelial cell line derived from a lymph node metastasis of non-small cell lung carcinoma, widely used as a model for metastatic lung adenocarcinoma. These cells retain key features of advanced lung cancer, including migratory and invasive capabilities, making them particularly suitable for investigating tumor cell dissemination.
DTNBP1 encodes dysbindin, a core subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin functions as a scaffold, interacting with BLOC1S1, BLOC1S2, SNAPIN, and PLDN to mediate cargo sorting and transport from endosomes to lysosomes and synaptic vesicles. Its expression is regulated by transcription factors such as TCF4 (downstream of Wnt signaling), SP1, NF-??B, and hypoxia. Downstream, dysbindin influences the trafficking of SNAP-25, syntaxin-1, VAMP2, PI4K2A, and the AP-3 complex, thereby modulating synaptic vesicle cycling and dopamine D2 receptor localization.
In the NCI-H1299 background, disruption of DTNBP1 disrupts intracellular trafficking pathways critical for both neuronal-like and cancer cell functions. Although NCI-H1299 cells are not neuronal, they express components of the trafficking machinery that overlap with neural processes; thus, DTNBP1 knockout serves as a useful model for vesicle trafficking defects implicated in schizophrenia and Hermansky-Pudlak syndrome type 7. Moreover, loss of dysbindin may impair lysosome-related organelle biogenesis and alter cell migration, providing a relevant system to study the role of vesicle trafficking in lung adenocarcinoma metastasis.
This polyclonal knockout cell population is well-suited for a range of experimental approaches, including western blotting, RT-qPCR, immunofluorescence, and co-immunoprecipitation to confirm dysbindin ablation and assess interacting partners. Functional assays such as migration and invasion assays, drug sensitivity screening, and vesicle recycling measurements can be employed to dissect trafficking-dependent phenotypes in cancer and neurobiology. Additionally, these cells can be used to screen small molecules targeting BLOC-1 complex function or dopamine receptor trafficking. For further technical information or to order this product, please contact Ascent Research.
