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Horm Metab Res 2007; 39(5): 336-340
DOI: 10.1055/s-2007-976538
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Alterations of Pancreatic Beta-cell Mass and Islet Number due to Ins2-controlled Expression of Cre Recombinase: RIP-Cre Revisited; Part 2

D. Pomplun 1 , 2 [♯] , S. Florian 1 [♯] , T. Schulz 1 , 2 , A. F. H. Pfeiffer 1 , M. Ristow 1 , 2
  • 1German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  • 2Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
Further Information

Publication History

received 30. 10. 2006

accepted 18. 12. 2006

Publication Date:
29 May 2007 (online)

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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.

Key words

diabetes - mouse models - cre-loxP - transgene - Cre recombinase - glucose metabolism - insulin secretion - islet of Langerhans - pancreatic beta cell - C57BL/6

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1 These authors contributed equally to this work.

Correspondence

M. Ristow

Department of Human Nutrition

Institute of Nutrition

University of Jena

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07743 Jena

Germany

Phone: +49/3641/949 63 0

Fax: +49/3641/949 63 2

Email: michael.ristow@mristow.org