ATXN1 Knouckout SK-HEP-1 Polyclonal Cells is a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human ATXN1 gene in the SK-HEP-1 liver adenocarcinoma cell line. This polyclonal knockout model, generated by CRISPR/Cas9-mediated gene disruption, eliminates functional ataxin-1 protein expression, enabling loss-of-function studies. The knockout product format ensures a heterogeneous population of edited cells, reflecting varied genetic modifications across the pool. This product is designed for research use in scientific investigations of ATXN1 biology and disease mechanisms.
The SK-HEP-1 host cell line is an established human liver adenocarcinoma line derived from ascites of a patient with liver adenocarcinoma. It exhibits adherent epithelial morphology and expresses endothelial markers, making it a widely used model for liver sinusoidal endothelial cells and hepatic adenocarcinoma studies. The cells provide a relevant hepatic microenvironment for examining gene function in liver-derived cellular contexts, offering a platform to explore interactions between ATXN1 loss and hepatic cellular phenotypes.
ATXN1 encodes ataxin-1, a transcriptional co-regulator and RNA-binding protein critical for cerebellar development and neuronal function. It operates within the CIC repressor complex, interacting directly with Capicua (CIC) and ATXN1-like (ATXN1L) to regulate gene transcription. ATXN1 is phosphorylated by AKT kinase, which modulates its stability and activity, and is targeted for degradation by the ubiquitin-proteasome system. Downstream, ATXN1-CIC complexes repress targets such as RORA, and ATXN1 recruits the SIN3A-HDAC complex to mediate transcriptional silencing. Additionally, it interacts with RNA-binding proteins including RBM17, PQBP1, and U2AF2, implicating it in RNA processing. Thus, ATXN1 acts as a hub linking phosphorylation-dependent signaling, transcriptional repression, and post-transcriptional control.
Disruption of ATXN1 in SK-HEP-1 cells abrogates ataxin-1 protein functions, perturbing its interactions with CIC and RNA-binding partners, which may alter neuronal gene expression programs and pathways associated with spinocerebellar ataxia type 1 (SCA1). Although ATXN1 is primarily known for its role in the cerebellum, its knockout in a hepatic cellular context enables investigation of non-neuronal functions and the impact of ataxin-1 loss on epithelial and endothelial biology. This model provides a unique tool to dissect ATXN1-dependent mechanisms without neuronal confounding factors, facilitating comparative studies in liver-derived cells.
This polyclonal ATXN1 knockout cell pool is suitable for diverse applications including loss-of-function phenotypic studies, SCA1 disease modeling in a heterologous system, and biochemical characterization of the ATXN1-CIC transcriptional complex. Researchers can employ techniques such as western blotting to confirm protein absence, RT-qPCR for mRNA quantification, immunofluorescence for localization analysis, co-immunoprecipitation to probe CIC interactions, and RNA-seq for transcriptome-wide impact assessment. Drug screening for SCA1 therapies and mapping of the ATXN1 interactome in human cells are additional uses. For further details on this CRISPR/Cas9-edited ATXN1 knockout SK-HEP-1 polyclonal cell population, please contact Ascent Research.
