Yipf5 Knockout INS-1 Cell Line

The Yipf5 Knockout INS-1 Cell Line is a CRISPR/Cas9-mediated gene-disrupted cell line derived from the rat insulinoma INS-1 background. This product provides a stable knockout model to investigate the role of YIPF5 in ER-to-Golgi vesicle-mediated transport and insulin secretion. By eliminating YIPF5 function, researchers can dissect COPII-dependent trafficking and its impact on beta-cell physiology under defined experimental conditions.

INS-1 cells are a widely used pancreatic beta-cell line established from an X-ray-induced rat insulinoma. They retain glucose-stimulated insulin secretion (GSIS) and express key beta-cell transcription factors such as PDX1, making them a relevant model for studying insulin regulation and metabolic stress. The cell line’s robust proliferative capacity and ease of genetic manipulation facilitate both mechanistic studies and high-throughput screening.

YIPF5 is a membrane-spanning receptor that anchors the COPII coat at ER exit sites, interacting with YIF1A and the SEC23-SEC24 subcomplex. It functions downstream of glucose stimulation and the ER stress signaling mediators XBP1 and ATF6, and is transcriptionally regulated by PDX1. YIPF5 couples cargo selection to vesicle budding, thereby controlling the trafficking of proinsulin processing intermediates and other secretory proteins. Knockout of Yipf5 disrupts ER-to-Golgi transport, triggering the unfolded protein response and impairing insulin maturation and secretion.

In the INS-1 context, Yipf5 deficiency models beta-cell dysfunction characteristic of type 2 diabetes, featuring ER stress activation and defective insulin release. This enables examination of how COPII trafficking defects contribute to beta-cell failure and how ER stress pathways are engaged. The model also supports investigation of pharmacological interventions aimed at restoring protein trafficking or mitigating ER stress in beta-cells.

This knockout cell line is suited for GSIS assays, western blotting for insulin and ER stress markers (BiP, CHOP), immunofluorescence analysis using ER (calnexin) and Golgi (GM130) markers, RT-qPCR for ER stress genes, and ultrastructural studies via transmission electron microscopy. Applications include dissecting COPII dynamics, studying diabetes pathogenesis, and screening therapeutic candidates targeting beta-cell dysfunction. For additional details, contact Ascent Research.