The AKR1C4 Knockout HAP1 Polyclonal Cells product is a CRISPR/Cas9-edited HAP1 cell population carrying targeted gene disruptions in AKR1C4. As a polyclonal knockout pool, it contains a variety of loss-of-function alleles, providing a robust model for studying the effects of AKR1C4 deficiency without clonal isolation.
HAP1 is a near-haploid human cell line derived from chronic myeloid leukemia (KBM-7), featuring an adherent, fibroblast-like morphology. Its haploidy simplifies genetic analysis, making it widely employed in functional genomics, drug screening, and CRISPR-based knockout studies.
AKR1C4 encodes an aldo-keto reductase that catalyses NADPH-dependent reduction of steroids and carbonyl compounds, thereby inactivating progesterone, androgens, and estrogens, and participating in bile acid biosynthesis. The gene is transcriptionally regulated by androgen receptor, estrogen receptor, steroidogenic factor-1, and farnesoid X receptor, and interacts with NADPH, steroid hormone substrates, and bile acid intermediates. AKR1C4 functionally cooperates with CYP17A1 and CYP3A4 in steroidogenic and xenobiotic pathways. Knockout disrupts these interactions, leading to altered steroid hormone profiles, dysregulated androgen/estrogen metabolism, and changes in bile acid profiles.
In HAP1 cells, AKR1C4 knockout provides a loss-of-function model to dissect hormone-dependent signaling and detoxification. Absence of AKR1C4 activity results in accumulation of active steroids, facilitating studies on hormone-driven proliferation and resistance in prostate and breast cancer. The model is also relevant to congenital adrenal hyperplasia, endometriosis, and metabolic disorders. The near-haploid background ensures clear genotype-phenotype correlations when investigating downstream targets such as steroid hormone levels and bile acid sensors.
Applications include steroid hormone metabolism studies using LC-MS profiling, cell proliferation assays for drug resistance testing in hormone-dependent cancers, and bile acid quantification for bile acid synthesis disorder research. The polyclonal knockout is also suitable for functional genomics screens and steroid receptor reporter gene assays. For more details, contact Ascent Research.
