Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Cell Biology, Endocrinology & Metabolism, PANCREATIC BETA-CELLS, NORMAL GLUCOSE-HOMEOSTASIS, INSULIN-SECRETION, PLACENTAL-LACTOGEN, PROLACTIN RECEPTOR, CRE RECOMBINASE, MICE, TRANSPORTER, LANGERHANS, PREGNANCY, Animals, Female, Human Growth Hormone, Humans, Islets of Langerhans, Male, Mice, Mice, Transgenic, Receptors, Prolactin, Tryptophan Hydroxylase, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, 3101 Biochemistry and cell biology, 3205 Medical biochemistry and metabolomics

Abstract:

The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-Cre(Late), RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-Cre(Late) mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.