The DMD Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the human renal clear cell adenocarcinoma cell line 786-O, featuring targeted disruption of the DMD gene leading to loss of dystrophin function. This knockout product is generated using CRISPR/Cas9-mediated gene editing, resulting in a heterogeneous pool of edited cells with impaired dystrophin expression. The polyclonal format provides a robust loss-of-function model without the clonal variability often associated with single-cell-derived lines, making it suitable for population-level studies of dystrophin function.
The parental 786-O cell line is a well-established epithelial model isolated from a primary renal clear cell adenocarcinoma. These cells harbor characteristic VHL mutations and exhibit constitutive HIF pathway activation, making them a standard system for renal cancer research, including tumorigenesis, metastasis, and drug resistance. This background provides a clinically relevant context for exploring dystrophin??s non-muscle functions, particularly its putative role as a tumor suppressor in epithelial cells.
Dystrophin is a large submembrane protein that links the actin cytoskeleton to the extracellular matrix through the dystrophin-glycoprotein complex (DGC). It interacts directly with actin and ??-dystroglycan, and associates with syntrophins, dystrobrevin, sarcoglycans, and neuronal nitric oxide synthase (nNOS). DMD expression is regulated by mechanical strain and transcription factors such as MyoD and SP1, as well as Wnt/??-catenin signaling. Downstream, dystrophin modulates nNOS localization, stabilizes the DGC, and influences MAPK and Akt signaling cascades, thereby controlling cell adhesion, migration, and mechanotransductive responses.
In the 786-O renal carcinoma background, DMD knockout disrupts the DGC and impairs cell-matrix adhesion, leading to altered cytoskeletal organization and mechanotransduction. This perturbation can impact tumor cell migration, invasion, and proliferation, consistent with dystrophin??s proposed tumor suppressor functions. By eliminating dystrophin in an epithelial cancer context, this model allows the dissection of DGC-mediated signaling in oncogenesis and the evaluation of dystrophin??s role in modulating cancer cell behavior.
This polyclonal knockout cell population is well-suited for a broad range of assays, including western blotting and immunofluorescence to validate dystrophin loss and DGC component mislocalization, cell adhesion and migration/invasion assays to assess functional phenotypes, co-immunoprecipitation for protein interaction studies, RNA-seq for transcriptomic analysis, and drug sensitivity testing for agents targeting dystrophin-related pathways. It enables screening of compounds for muscular dystrophy and probing the interplay between DGC signaling and oncogenic networks. For more information or custom requests, contact Ascent Research.
