RT Journal Article SR Electronic T1 Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.23.441054 DO 10.1101/2021.04.23.441054 A1 Elisabeth Kemter A1 Andreas Müller A1 Martin Neukam A1 Anna Ivanova A1 Nikolai Klymiuk A1 Simone Renner A1 Kaiyuan Yang A1 Johannes Broichhagen A1 Mayuko Kurome A1 Valerie Zakhartchenko A1 Barbara Kessler A1 Klaus-Peter Knoch A1 Marc Bickle A1 Barbara Ludwig A1 Kai Johnsson A1 Heiko Lickert A1 Thomas Kurth A1 Eckhard Wolf A1 Michele Solimena YR 2021 UL http://biorxiv.org/content/early/2021/04/23/2021.04.23.441054.1.abstract AB β-cells produce, store and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β-cell function is mostly derived from studies of ex vivo isolated islets and/or rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.Competing Interest StatementThe authors have declared no competing interest.