The BCL2L11 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the BCL2L11 gene in the 786-O renal cell adenocarcinoma line. This polyclonal pool provides a heterogeneous loss-of-function model for the pro-apoptotic BH3-only protein BIM, eliminating its expression across the population. The cells are supplied as a live population, ready for functional studies.
The 786-O cell line is a VHL-mutant model of clear cell renal cell carcinoma (ccRCC), characterized by biallelic VHL inactivation leading to constitutive HIF stabilization, angiogenesis, and metabolic reprogramming. This background is widely used to study ccRCC biology and VHL pathway interactions with apoptotic networks.
BCL2L11 encodes BIM, a BH3-only protein that initiates intrinsic apoptosis by neutralizing anti-apoptotic BCL2, BCL-XL, and MCL1, and directly activating BAX and BAK, resulting in mitochondrial outer membrane permeabilization, cytochrome c release, and caspase-9/APAF-1 apoptosome formation. BIM is transcriptionally activated by FOXO3a and CHOP, and upregulated by TGF-?? and growth factor withdrawal, serving as a central stress sensor.
In 786-O cells, BIM knockout offers a tool to examine apoptotic resistance in VHL-deficient ccRCC. It allows dissection of BIM-dependent cell death and investigation of how VHL loss modulates apoptotic thresholds. The model is instrumental for assessing BH3 mimetic sensitivity and the role of BIM in drug resistance.
Applications include apoptosis signaling studies, BH3 mimetic screening (e.g., ABT-263, A-1331852, S63845), and drug resistance profiling using assays such as Western blot, Annexin V/PI flow cytometry, cell viability, cytochrome c ELISA, caspase activity, and co-immunoprecipitation. Contact Ascent Research for more information.
