title: Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone.
abstract: There is growing concern over confounding artifacts associated with β-cell-specific Cre-recombinase transgenic models, raising questions about their general usefulness in research. The inducible β-cell-specific transgenic (MIP-CreERT(1Lphi)) mouse was designed to circumvent many of these issues, and we investigated whether this tool effectively addressed concerns of ectopic expression and disruption of glucose metabolism. Recombinase activity was absent from the central nervous system using a reporter line and high-resolution microscopy. Despite increased pancreatic insulin content, MIP-CreERT mice on a chow diet exhibited normal ambient glycemia, glucose tolerance and insulin sensitivity, and appropriate insulin secretion in response to glucose in vivo and in vitro. However, MIP-CreERT mice on different genetic backgrounds were protected from high-fat/ streptozotocin (STZ)-induced hyperglycemia that was accompanied by increased insulin content and islet density. Ectopic human growth hormone (hGH) was highly expressed in MIP-CreERT islets independent of tamoxifen administration. Circulating insulin levels remained similar to wild-type controls, whereas STZ-associated increases in α-cell number and serum glucagon were significantly blunted in MIP-CreERT(1Lphi) mice, possibly due to paracrine effects of hGH-induced serotonin expression. These studies reveal important new insight into the strengths and limitations of the MIP-CreERT mouse line for β-cell research.
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oropeza
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jouvet
authors.affiliation: Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Lionel
authors.initials: L
authors.lastname: Budry
authors.affiliation: Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Campbell
authors.affiliation: Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada Département de Médecine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Bouyakdan
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Lacombe
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Perron
authors.affiliation: Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada Département de Médecine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Bergeron
authors.affiliation: Department of Medicine and Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Neuman
authors.affiliation: Department of Medicine and Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Harpreet K
authors.initials: HK
authors.lastname: Brar
authors.affiliation: Department of Medicine and Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Fenske
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Clemence
authors.initials: C
authors.lastname: Meunier
authors.affiliation: Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sczelecki
authors.affiliation: Department of Medicine and Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kimple
authors.affiliation: Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
authors.affiliation: Department of Cellular and Molecular Medicine, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Screaton
authors.affiliation: Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada Département de Médecine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Poitout
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada Division of Experimental Medicine, McGill University, Montreal, QC, Canada Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ferron
authors.affiliation: Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada Département de Médecine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Alquier
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada Division of Experimental Medicine, McGill University, Montreal, QC, Canada Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada Département de Médecine, Université de Montréal, Montreal, QC, Canada jennifer.estall@ircm.qc.ca.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Estall
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019382:Human Growth Hormone