BDH1 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for targeted disruption of the BDH1 gene in human cells. This product provides a loss-of-function model for investigating the role of BDH1 (3-hydroxybutyrate dehydrogenase 1) in ketone body metabolism. BDH1 catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, a reaction central to hepatic ketogenesis and extrahepatic ketolysis. The polyclonal nature of this knockout population ensures a diverse array of edited alleles, facilitating population-level studies of gene function without clonal selection bias.
The host cell line, HAP1, is a near-haploid human chronic myeloid leukemia (CML) cell line derived from the KBM-7 line. HAP1 cells grow in suspension and possess a mostly haploid karyotype, making them exceptionally suited for genetic screens, particularly CRISPR-based functional genomics studies. Their haploid nature minimizes genetic redundancy, enabling clear phenotype-genotype correlations upon gene disruption. Widely adopted in biomedical research, HAP1 cells provide a robust platform for studying gene function in cancer cell biology, signal transduction, and metabolic pathways.
Mechanistically, BDH1 functions centrally in ketone body metabolism, interacting with ACAT1, HMGCS2, and OXCT1. Its expression is driven by PPARA and HNF4A, while enzymatic activity is modulated by insulin, glucagon, and the cAMP/PKA pathway. The reaction generates acetoacetate and NADH, impacting mitochondrial redox state and TCA cycle flux. This in turn affects FOXO3a-mediated transcriptional programs, linking nutrient status to stress adaptation. BDH1 thereby coordinates systemic energy homeostasis during fasting and nutrient deprivation.
In HAP1 leukemic cells, BDH1 knockout enables dissection of ketone body utilization in cancer metabolism, where altered metabolic dependencies are common. Disruption of BDH1 may impair the use of ketone bodies as fuels, sensitizing cells to metabolic stress. This model is relevant for diabetic ketoacidosis, metabolic syndrome, cancer cachexia, and ketotic hypoglycemia. The haploid HAP1 background allows unambiguous assessment of BDH1-dependent vulnerabilities.
Typical applications include metabolic flux analysis using Seahorse assays, quantification of ketone body levels, and assessment of cell viability under nutrient-restricted conditions. Western blotting and RT-qPCR enable verification of BDH1 loss and downstream effects. This knockout model is suitable for drug screening targeting metabolic disorders and for global transcriptomic and metabolomic profiling via RNA-seq and mass spectrometry. With BDH1 Knockout HAP1 Polyclonal Cells, researchers can advance investigations into mitochondrial function, cancer metabolism, and diabetes. For further information, please contact Ascent Research.
