Impaired Islet Function in Commonly Used Transgenic Mouse Lines due to Human Growth Hormone Minigene Expression

• DOI: 10.1016/j.cmet.2014.11.004
• Publication Date: 2014-12-02T17:00:39Z
• Authors: Bas Brouwers; Geoffroy de Faudeur; Anna B. Osipovich; Lotte Goyvaerts; Katleen Lemaire; Leen Boesmans; Elisa J.G. Cauwelier; Mikaela Granvik; Vincent P.E.G. Pr...; Leentje Van Lommel; Jolien Van Schoors; Jennifer S. Stancill; Ilse Smolders; Vincent Goffin; Nadine Binart; Peter in’t Veld; Jeroen Declercq; Mark A. Magnuson; John W.M. Creemers; Frans Schuit; Anica Schraenen
• Keywords: Male; 0301 basic medicine; mice; Physiology; Human Growth Hormone; Receptors, Prolactin; Mice, Transgenic; Cell Biology; Tryptophan Hydroxylase; Islets of Langerhans; Mice; 03 medical and health sciences; Animals; Humans; Female; islets of Langerhans; Molecular Biology

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.