The HSD17B12 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population targeting the HSD17B12 gene in the near-haploid human chronic myeloid leukemia cell line HAP1. This product provides a heterogeneous pool of cells harboring gene disruptions at the HSD17B12 locus, enabling loss-of-function studies without the need for single-cell cloning. The polyclonal format offers a robust and representative model for analyzing the functional consequences of HSD17B12 ablation in an isogenic genetic background.
HAP1 cells are derived from the KBM-7 chronic myeloid leukemia line and possess a near-haploid karyotype, making them exceptionally suited for knockout screens and genome-wide loss-of-function analyses. Their haploid nature ensures that a single CRISPR/Cas9 targeting event can eliminate gene function in most cells, facilitating clean phenotypic assessment. Widely adopted in functional genomics, HAP1 cells support efficient gene editing and are compatible with high-throughput screening platforms, which accelerates the functional characterization of genes like HSD17B12.
HSD17B12 encodes a bifunctional enzyme pivotal to both steroid hormone metabolism and very long-chain fatty acid (VLCFA) elongation. In estrogen biosynthesis, it catalyzes the reduction of estrone to the potent estrogen estradiol, thereby promoting estrogen receptor (ESR1 and ESR2) signaling and the transcriptional activation of estrogen-responsive genes such as GREB1 and TFF1. This activity is regulated by factors including estrogen receptor alpha (ESR1), peroxisome proliferator-activated receptors (PPARs), and sterol regulatory element-binding protein 1 (SREBP1). In parallel, HSD17B12 functions as a 3-ketoacyl-CoA reductase within the fatty acid elongation cycle, interacting with elongases ELOVL6 and ELOVL7 to produce very long-chain fatty acids essential for the synthesis of complex lipids, including ceramides and sphingolipids. The coordinated dual functionality places HSD17B12 at a critical node linking hormonal and lipid metabolic networks.
Disruption of HSD17B12 in the haploid HAP1 background offers a precise genetic system to dissect its bifurcated roles. Loss of estradiol production can be directly assessed by quantifying estradiol levels via ELISA or LC-MS, while downstream estrogen signaling can be monitored through quantitative RT?PCR of target genes. Concurrently, the impact on VLCFA elongation is amenable to lipidomics profiling, revealing alterations in very long-chain fatty acyl?CoAs and downstream ceramides. This model is particularly valuable for studying the interplay between endocrine signaling and lipid metabolism, with implications for diseases such as estrogen?sensitive cancers and metabolic syndromes. The haploid context minimizes confounding by wild?type alleles, ensuring a clear interpretation of the knockout phenotype.
Researchers can employ these polyclonal knockout cells in a variety of experimental paradigms, including functional genomics screens to identify synthetic lethal interactions, drug target validation for endocrine and metabolic disorders, and mechanistic studies of hormone?driven carcinogenesis. Representative assays such as proliferation assays in estrogen?sensitive cancer cell lines, combined with estradiol quantification and lipidomics, provide a multi?layered view of HSD17B12 function. The polyclonal pool also serves as a stable source material for subsequent clonal selection if homogeneous knockout populations are desired. For further technical details, bulk pricing, or custom requests, please contact Ascent Research.
