title: RIP-Cre revisited, evidence for impairments of pancreatic beta-cell function.
abstract: The Cre/loxP recombinase system for performing conditional gene targeting experiments has been very useful in exploring genetic pathways that control both the development and function of pancreatic beta-cells. One particular line of transgenic mice (B6.Cg-Tg(Ins2-cre)25Mgn/J), commonly called RIP-Cre, in which expression of Cre recombinase is controlled by a short fragment of the rat insulin II gene promoter has been used in at least 21 studies on at least 17 genes. In most of these studies inactivation of the gene of interest was associated with either glucose intolerance or frank diabetes. Experimental evidence has been gradually emerging to suggest that RIP-Cre mice alone display glucose intolerance. In this study experiments from three laboratories demonstrate that RIP-Cre mice, in the absence of genes targeted by loxP sites, are glucose intolerant, possibly due to impaired insulin secretion. In addition, we review the use of RIP-Cre mice and discuss possible molecular underpinnings and ramifications of our findings.
authors.affiliation: Laboratory of Genetics and Physiology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.forename: Xueying
authors.initials: X
authors.lastname: Lin
authors.forename: Morris F
authors.initials: MF
authors.lastname: White
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D005260:Female; D018390:Gene Targeting; D018149:Glucose Intolerance / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D019426:Integrases / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D007328:Insulin; C045073:Cre recombinase; D019426:Integrases