The JAGN1 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the JAGN1 gene has been disrupted in the human A-549 lung adenocarcinoma cell line. This loss-of-function model enables investigation of JAGN1??s roles in endoplasmic reticulum (ER) homeostasis, glycoprotein processing, and downstream signaling pathways within a widely used epithelial background. The polyclonal format, comprising a mixture of edited alleles, facilitates robust functional studies without the need for single-cell clone isolation.
The A-549 host cell line originates from a lung adenocarcinoma of a 58-year-old male and serves as a well-characterized model for alveolar type II epithelial cells. These cells display adherent growth, high proliferative capacity, and are extensively employed in lung cancer biology, drug discovery, and investigations of epithelial cell responses to ER stress and chemotherapeutic agents.
JAGN1 encodes an ER-resident transmembrane protein essential for normal neutrophil differentiation and ER homeostasis. It interacts with key quality-control components including calnexin (CANX), the oligosaccharyltransferase subunit STT3B, and UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), and is transcriptionally regulated by CCAAT/enhancer-binding protein alpha (CEBPA) and activating transcription factor 6 (ATF6). JAGN1 disruption triggers the unfolded protein response (UPR), as evidenced by upregulation of ATF6, X-box binding protein 1 (XBP1), heat shock protein family A member 5 (HSPA5/BiP), endoplasmic reticulum to nucleus signaling 1 (ERN1/IRE1??), and eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3/PERK). This stress response impairs N-glycan biosynthesis mediated by the STT3A/B complex, CANX, and UGGT1, and consequently reduces expression of downstream effectors including integrin alpha M (ITGAM), myeloperoxidase (MPO), and interleukin-8 (IL-8). The resulting defects in protein glycosylation and enhanced apoptosis mirror the pathogenesis of severe congenital neutropenia and bone marrow failure.
In the A-549 epithelial context, JAGN1 knockout provides a unique non-hematopoietic model to dissect ER stress and glycosylation pathways that are increasingly implicated in lung cancer progression, chemoresistance, and immune evasion. It allows researchers to model congenital neutropenia-associated mechanisms without the confounding influence of hematopoietic differentiation, and offers a platform to examine how disruption of ER homeostasis affects lung carcinoma cell proliferation, migration, and sensitivity to ER stress-inducing agents such as tunicamycin.
Experimental applications include confirmation of JAGN1 disruption by western blot and RT-qPCR, monitoring ER stress markers (BiP, CHOP), lectin-based glycosylation profiling, apoptosis detection via Annexin V staining, wound healing migration assays, and drug sensitivity testing. This model supports investigations into UPR signaling, glycoprotein processing defects, congenital neutropenia pathways, and therapeutic strategies for lung cancer. For further details or to customize this product, please contact Ascent Research.
