Year: 2010
Type: article
Abstract: OBJECTIVE: Conditional gene targeting has been extensively used for in vivo analysis of gene function in β-cell biology. The objective of this study was to examine whether mouse transgenic Cre lines, used to mediate β-cell- or pancreas-specific recombination, also drive Cre expression in the brain. RESEARCH DESIGN AND METHODS: Transgenic Cre lines driven by Ins1, Ins2, and Pdx1 promoters were bred to R26R reporter strains. Cre activity was assessed by β-galactosidase or yellow fluorescent protein expression in the pancreas and the brain. Endogenous Pdx1 gene expression was monitored using Pdx1(tm1Cvw) lacZ knock-in mice. Cre expression in β-cells and co-localization of Cre activity with orexin-expressing and leptin-responsive neurons within the brain was assessed by immunohistochemistry. RESULTS: All transgenic Cre lines examined that used the Ins2 promoter to drive Cre expression showed widespread Cre activity in the brain, whereas Cre lines that used Pdx1 promoter fragments showed more restricted Cre activity primarily within the hypothalamus. Immunohistochemical analysis of the hypothalamus from Tg(Pdx1-cre)(89.1Dam) mice revealed Cre activity in neurons expressing orexin and in neurons activated by leptin. Tg(Ins1-Cre/ERT)(1Lphi) mice were the only line that lacked Cre activity in the brain. CONCLUSIONS: Cre-mediated gene manipulation using transgenic lines that express Cre under the control of the Ins2 and Pdx1 promoters are likely to alter gene expression in nutrient-sensing neurons. Therefore, data arising from the use of these transgenic Cre lines must be interpreted carefully to assess whether the resultant phenotype is solely attributable to alterations in the islet β-cells.
Source: Diabetes
DOI: 10.2337/db10-0624
Authors: Barton Wicksteed, Marcela Brissova, Wenbo Yan, Darren M. Opland, Jennifer L. Plank, Rachel B. Reinert, Lorna M. Dickson, Natalia A. Tamarina, Louis H. Philipson, Alena Shostak, Ernesto Bernal-Mizrachi, Lynda Elghazi, Michael W. Roe, Patricia A. Labosky, Martin G. Myers, Maureen Gannon, Alvin C. Powers, Peter J. Dempsey
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: American Diabetes Association, U.S. Department of Veterans Affairs, American Heart Association, Vanderbilt University, University of Chicago, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Neural crest formation and maintenance of multipotency, G1149166549, G117257630, G1309980231, Pancreatic Islet Imaging and Blood Flow, Michigan Diabetes Research and Training Center, HNF6 Function in the Pancreatic Endocrine Lineage, G2304076072, Nutrient signals and programming of pancreas development, Molecular Mechanisms of Human and Murine Beta Cell Proliferation and Regeneration, G2906896244, G2940777275, GLP-1 to Enhance Islet Transplantation, G3496579536, G3760333202, G393281165, Vanderbilt Mouse Metabolic Phenotyping Center, G4133317455, Foxm 1b in Endocrine Pancreas Growth and Regeneration, Calcium Signaling in Pancreatic Beta Cell Endoplasmic Reticulum, VEGF and Islet Vascularization, Developmental Mechanisms of Leptin Resistance, G6845279160, GLP-1 to Enhance Islet Transplantation, AKT/mTOR signaling and regulation of cell cycle in B-cells, Diabetes Research and Training Center, Foxm 1b endocrine pancreas growth and regeneration, Coordinating Center for Beta Cell Biology Consortium, Diabetes Research and Training Center, G9000001850, G9000002043, G9000052735, Multidisciplinary Training in Molecular Endocrinology, G9000231012, G9000231952, Vanderbilt Diabetes Research Center, Endogenous Betacellulin Signaling in Beta-cell Biology
OpenAlex ID: W2120647714