Published in:
Open Access 01-03-2015 | Article
Ins1 Cre knock-in mice for beta cell-specific gene recombination
Published in: Diabetologia | Issue 3/2015
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Aims/hypothesis
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.
Methods
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.
Results
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.
Conclusions/interpretation
These two strains of deleter mice are useful new resources to investigate the molecular physiology of pancreatic beta cells.