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

Abstract:

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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Thorens B,Tarussio D,Maestro MA,Rovira M,Heikkilä E,Ferrer J

doi

10.1007/s00125-014-3468-5

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

558-65

issue

3

eissn

0012-186X

issn

1432-0428

journal_volume

58

pub_type

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