Abstract

The beta cell of the endocrine pancreas play a critical role in the pathogenesis of diabetes mellitus. A comprehensive understanding of the molecular basis of beta cell development and function should lead to new approaches for the prevention and treatment of diabetes. The overall goal of this application is the generation of genetically-defined mouse models that will facilitate the identification. The overall goal of this application is the generation of genetically-defined mouse models that will facilitate the identification and purification of pancreatic stem/progenitor cells.
The aims of this application are to generate transgenic mouse models in which green fluorescent protein (GFP) and its cyan and yellow derivatives as well as DsRed fluorescent protein (DsRed) are driven by different developmentally-regulated promoters including those of the transcription factors insulin promoter factor-1, neurogenin 3 and Pax4, and the pancreatic hormones insulin and glucagon. These mouse models will be used to isolate and characterize presumptive pancreatic stem/progenitor cells. We believe these animal models will be a valuable resource for members of the Beta Cell Biology Consortium and will facilitate the identification and characterization of pancreatic stem/progenitor cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19DK061245-02
Application #
6651342
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2002-09-30
Project End
2003-07-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Lancman, Joseph J; Zvenigorodsky, Natasha; Gates, Keith P et al. (2013) Specification of hepatopancreas progenitors in zebrafish by hnf1ba and wnt2bb. Development 140:2669-79
Ohta, Yasuharu; Kosaka, Yasuhiro; Kishimoto, Nina et al. (2011) Convergence of the insulin and serotonin programs in the pancreatic ?-cell. Diabetes 60:3208-16
Kalousova, Anna; Mavropoulos, Anastasia; Adams, Bruce A et al. (2010) Dachshund homologues play a conserved role in islet cell development. Dev Biol 348:143-52
Kim, Hail; Toyofuku, Yukiko; Lynn, Francis C et al. (2010) Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med 16:804-8
Smith, Stuart B; Qu, Hui-Qi; Taleb, Nadine et al. (2010) Rfx6 directs islet formation and insulin production in mice and humans. Nature 463:775-80
Uchizono, Yuji; Baldwin, Aaron C; Sakuma, Hiroya et al. (2009) Role of HNF-1alpha in regulating the expression of genes involved in cellular growth and proliferation in pancreatic beta-cells. Diabetes Res Clin Pract 84:19-26
Chung, Won-Suk; Stainier, Didier Y R (2008) Intra-endodermal interactions are required for pancreatic beta cell induction. Dev Cell 14:582-93
Dong, P Duc Si; Provost, Elayne; Leach, Steven D et al. (2008) Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas. Genes Dev 22:1445-50
Hara, M; Shen, J; Pugh, W et al. (2007) Sustained expression of hepatocyte nuclear factor-6 leads to loss of pancreatic beta-cells by apoptosis. Exp Clin Endocrinol Diabetes 115:654-61
Lynn, F C; Smith, S B; Wilson, M E et al. (2007) Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci U S A 104:10500-5

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