The DHRS3 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte line, with targeted disruption of the human DHRS3 gene, which encodes a retinaldehyde reductase controlling retinoic acid synthesis. The polyclonal nature provides a heterogeneous pool of edited alleles, reducing clonal variability and supporting reliable loss-of-function studies.
The Raji cell line is an EBV-positive B lymphocyte line derived from a patient with Burkitt’s lymphoma, widely used as a model for B-cell lymphomagenesis. It exhibits characteristic features such as high proliferative rate and B-cell marker expression, and its EBV status is relevant for virus-host interaction studies. In this genetic background, DHRS3 disruption allows exploration of retinoid metabolism in lymphoma biology.
DHRS3 encodes a short-chain dehydrogenase/reductase that catalyzes the NADPH-dependent reduction of all-trans-retinal to all-trans-retinol, acting as a gatekeeper for retinoic acid (RA) synthesis. By restricting retinaldehyde availability for oxidation by aldehyde dehydrogenases ALDH1A2/ALDH1A3, DHRS3 limits RA production. Loss of DHRS3 elevates RA levels, which then activates nuclear receptors RAR?? and RXR, leading to transcription of RARE-containing target genes such as HOX genes and RAR??. DHRS3 itself is regulated by retinoic acid, PPAR??, C/EBP??, and insulin, forming a feedback loop that fine-tunes retinoid signaling and downstream effects including PPAR?? target modulation.
In B-cell lymphoma models, retinoids exhibit anti-proliferative and differentiation-inducing properties. By ablating DHRS3, this knockout system shifts the balance toward RA excess, offering a tool to dissect how RA/RAR/RXR signaling influences lymphoma cell fate. The interaction between RA and PPAR?? pathways, both implicated in metabolism and proliferation, can be interrogated in this isogenic Raji background, shedding light on synergistic or antagonistic effects.
Applications include RT-qPCR and western blotting for DHRS3 expression, LC-MS-based quantitation of retinoic acid, RARE-luciferase reporter assays for RAR/RXR activity, flow cytometric analysis of differentiation markers, and cell proliferation assays. Transcriptomic profiling (RNA-seq) and ChIP-qPCR for RAR binding can map genome-wide regulatory responses. Drug screening for retinoid pathway modulators is also facilitated. For further information, please contact Ascent Research.
