title: Impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression.
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.
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Bas
authors.initials: B
authors.lastname: Brouwers
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: de Faudeur
authors.affiliation: Center for Stem Cell Biology and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Osipovich
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Lotte
authors.initials: L
authors.lastname: Goyvaerts
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Boesmans
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Elisa J G
authors.initials: EJ
authors.lastname: Cauwelier
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Granvik
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Vincent P E G
authors.initials: VP
authors.lastname: Pruniau
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.affiliation: Center for Neurosciences, Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels 1090, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Van Schoors
authors.affiliation: Center for Stem Cell Biology and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Stancill
authors.affiliation: Center for Neurosciences, Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels 1090, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.affiliation: INSERM U845, Research Center Growth and Signaling, PRL/GH Pathophysiology Laboratory, Faculty of Medicine, University Paris Descartes, Sorbonne Paris Cité, Paris 75993, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goffin
authors.affiliation: INSERM U693, Faculté de Médecine Paris-Sud, University Paris-Sud, Le Kremlin-Bicêtre 94276, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels 1090, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: in't Veld
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Declercq
authors.affiliation: Center for Stem Cell Biology and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium. Electronic address: john.creemers@med.kuleuven.be.
authors.forename: John W M
authors.initials: JW
authors.lastname: Creemers
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium. Electronic address: frans.schuit@med.kuleuven.be.
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven 3000, Belgium.
authors.forename: Anica
authors.initials: A
authors.lastname: Schraenen
mesh_terms: D000818:Animals; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D011981:Receptors, Prolactin; D019382:Human Growth Hormone; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase