Jeroen Declercq, Nadine Binart, Leentje Van Lommel, Frans Schuit, Leen Boesmans, Vincent P. E. G. Pruniau, Katleen Lemaire, Anica Schraenen, Anna B. Osipovich, Mark A. Magnuson, Jennifer S. Stancill, Lotte Goyvaerts, Bas Brouwers, Vincent Goffin, Mikaela Granvik, John W.M. Creemers, Jolien Van Schoors, Elisa J.G. Cauwelier, Peter In 'T Veld, Geoffroy de Faudeur, Ilse Julia Smolders, Medical Biochemistry, Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, Pathology/molecular and cellular medicine, and Diabetes Pathology & Therapy
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. publisher: Elsevier articletitle: Impaired Islet Function in Commonly Used Transgenic Mouse Lines due to Human Growth Hormone Minigene Expression journaltitle: Cell Metabolism articlelink: http://dx.doi.org/10.1016/j.cmet.2014.11.004 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved. ispartof: Cell Metabolism vol:20 issue:6 pages:979-990 ispartof: location:United States status: published