Ins1(Cre) knock-in mice for beta cell-specific gene recombination

Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy...

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Veröffentlicht in:Diabetologia 2015-03, Vol.58 (3), p.558-565
Hauptverfasser: Thorens, Bernard, Tarussio, David, Maestro, Miguel Angel, Rovira, Meritxell, Heikkilä, Eija, Ferrer, Jorge
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container_issue 3
container_start_page 558
container_title Diabetologia
container_volume 58
creator Thorens, Bernard
Tarussio, David
Maestro, Miguel Angel
Rovira, Meritxell
Heikkilä, Eija
Ferrer, Jorge
description Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy of major forms of diabetes. Selective gene inactivation in pancreatic beta cells, using the Cre-lox system, is a powerful approach to assess the role of particular genes in beta cells and their impact on whole body glucose homeostasis. Several Cre recombinase (Cre) deleter mice have been established to allow inactivation of genes in beta cells, but many show non-specific recombination in other cell types, often in the brain. We describe the generation of Ins1(Cre) and Ins1(CreERT2) mice in which the Cre or Cre-oestrogen receptor fusion protein (CreERT2) recombinases have been introduced at the initiation codon of the Ins1 gene. We show that Ins1(Cre) mice induce efficient and selective recombination of floxed genes in beta cells from the time of birth, with no recombination in the central nervous system. These mice have normal body weight and glucose homeostasis. Furthermore, we show that tamoxifen treatment of adult Ins1(CreERT2) mice crossed with Rosa26-tdTomato mice induces efficient recombination in beta cells. These two strains of deleter mice are useful new resources to investigate the molecular physiology of pancreatic beta cells.
doi_str_mv 10.1007/s00125-014-3468-5
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subjects Animals
Female
Glucose Tolerance Test
Insulin - genetics
Insulin - metabolism
Insulin-Secreting Cells - metabolism
Integrases - genetics
Integrases - metabolism
Male
Mice
Mice, Mutant Strains
title Ins1(Cre) knock-in mice for beta cell-specific gene recombination
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