title: Alterations of pancreatic beta-cell mass and islet number due to Ins2-controlled expression of Cre recombinase: RIP-Cre revisited; part 2.
abstract: Tissue-specific disruption of genes by targeted expression of Cre recombinase in insulin-producing cells has been widely used to explore pathways involved in regulation of pancreatic beta-cell mass. One particular line of transgenic mice [B6.Cg-Tg(Ins2-cre)25Mgn/J], commonly called RIP-Cre, in which the expression of Cre recombinase is controlled by a short fragment of the rat insulin II gene promoter has been used on at least 20 genes in at least 27 studies. In the majority of these studies (15 out of 27) inactivation of the gene of interest was associated with alterations in islet architecture, islet mass, or pancreatic insulin content. We have tested the hypothesis that genomic integration or expression of Cre recombinase alone causes alterations of beta-cell mass by quantifying islet number and mass in RIP-Cre mice. We have observed a significant hypoplasia of beta-cells in young RIP-Cre mice, and a significant hyperplasia of islets in older RIP-Cre animals. These findings suggest that glucose intolerance and impaired insulin secretion previously described for younger RIP-Cre mice might be caused by transgene-associated islet hypoplasia, and that hyperplasia in older mice might reflect a compensatory response to transgene-related glucose intolerance.
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Pomplun
authors.forename: S
authors.initials: S
authors.lastname: Florian
authors.forename: T
authors.initials: T
authors.lastname: Schulz
authors.forename: A F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: M
authors.initials: M
authors.lastname: Ristow
mesh_terms: D000818:Animals; D005260:Female; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology* / Q000648:ultrastructure; D019426:Integrases / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019076:Transgenes / Q000235:genetics
chemical_list: D007328:Insulin; C045073:Cre recombinase; D019426:Integrases