The APOE Knockout HAP1 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population of HAP1 cells that harbor targeted disruptions in the APOE gene, resulting in a loss-of-function model for apolipoprotein E research. This heterogeneous pool eliminates clonal selection artifacts and provides a robust system for functional studies, biochemical assays, and pathway investigation. The gene disruption is achieved via CRISPR/Cas9-mediated editing, ensuring efficient knockout across the population without the need for single-cell expansion.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia line, exhibiting fibroblast-like morphology and a predominantly haploid karyotype. This genetic simplicity makes HAP1 an ideal host for knockout studies, as disruption of a single allele yields a clear null phenotype, facilitating unambiguous genotype-phenotype correlations. HAP1 cells are widely employed in genetic screening, signal transduction research, and drug discovery due to their stable near-haploid genome and ease of manipulation.
APOE encodes apolipoprotein E, a critical component of lipoprotein particles that mediates lipid transport by binding to LDL receptor family members LDLR, LRP1, and VLDLR, as well as heparan sulfate proteoglycans. ApoE is essential for cholesterol homeostasis and phospholipid trafficking, and in the central nervous system, it influences amyloid-beta clearance, with the ??4 isoform conferring elevated Alzheimer’s disease risk. APOE expression is transcriptionally regulated by LXR, PPAR??, and c/EBP, and is modulated by inflammatory cytokines including TNF?? and IL-1??. ApoE promotes cholesterol efflux via ABCA1 and facilitates receptor-mediated endocytosis of lipoproteins, linking it to both lipid metabolism and neuroinflammation.
In the HAP1 background, APOE knockout provides a clean model to dissect ApoE-dependent lipid handling and signaling without confounding endogenous protein. The near-haploid genome ensures complete loss of APOE expression, avoiding compensatory effects seen in diploid lines. HAP1 cells express the lipoprotein uptake machinery, enabling studies of receptor-mediated clearance and cholesterol trafficking. This model is suited for high-throughput screening of ApoE modulators and investigation of crosstalk between lipid metabolism and inflammatory pathways relevant to cardiovascular and neurodegenerative diseases.
Key research applications include Alzheimer’s disease modeling, cholesterol metabolism studies, drug screening, and neurodegeneration research. Representative assays include western blotting for APOE isoforms, ELISA for ApoE secretion, cholesterol efflux and LDL uptake assays, amyloid-beta aggregation measurements, immunofluorescence for lipid droplets, and RT-qPCR for transcriptional analysis. The polyclonal knockout population is well-suited to pooled screening and functional genomics. For further information, researchers may contact Ascent Research.
