Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping - PubMed
3 hours ago
- #genetic mapping
- #CRISPR screen
- #proinsulin regulation
- A genome-wide CRISPR screen identified 84 proinsulin regulators that affect the intracellular proinsulin/insulin ratio in mouse β-cells, distinguishing them from insulin regulators.
- Functional analysis emphasizes the Golgi as the primary organelle for proinsulin storage and regulation, with trafficking dynamics influencing proinsulin levels.
- Protein disulfide isomerase Pdia6 emerged as a key regulator from both CRISPR screening and in vivo QTL mapping, affecting proinsulin accumulation without impacting folding.
- Mouse QTL mapping linked plasma proinsulin levels to genetic loci, with CRISPR data helping identify causal genes like Pdia6.
- Pdia6 depletion in human and mouse β-cells reduces proinsulin production through a UPR-independent mechanism, offering insights into proinsulin/insulin homeostasis.