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Cell Metab. 2014 Dec 2;20(6):979-90. doi: 10.1016/j.cmet.2014.11.004.

Impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression.

Author information

1
Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
2
Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
3
Center for Stem Cell Biology and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
4
Center for Neurosciences, Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels 1090, Belgium.
5
INSERM U845, Research Center Growth and Signaling, PRL/GH Pathophysiology Laboratory, Faculty of Medicine, University Paris Descartes, Sorbonne Paris Cité, Paris 75993, France.
6
INSERM U693, Faculté de Médecine Paris-Sud, University Paris-Sud, Le Kremlin-Bicêtre 94276, France.
7
Diabetes Research Center, Vrije Universiteit Brussel, Brussels 1090, Belgium.
8
Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium. Electronic address: john.creemers@med.kuleuven.be.
9
Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium. Electronic address: frans.schuit@med.kuleuven.be.

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.

PMID:
25470546
PMCID:
PMC5674787
DOI:
10.1016/j.cmet.2014.11.004
[Indexed for MEDLINE]
Free PMC Article

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