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Title page for ETD etd-12042009-090812


Type of Document Master's Thesis
Author Kantz, Jeannelle Alexandria
URN etd-12042009-090812
Title The role of vascular endothelial growth factor-A (VEGF-A) in pancreatic islet function in adults
Degree Master of Science
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Maureen Gannon Committee Member
Owen P. McGuinness Committee Member
Keywords
  • VEGF-A
Date of Defense 2009-05-22
Availability unrestricted
Abstract
MOLECULAR PHYSIOLOGY AND BIOPHYSICS

The Role of Vascular Endothelial Growth Factor-A (VEGF-A) in Pancreatic Islet Function

in Adults

JEANNELLE A. KANTZ

Thesis under the direction of Professor Dr. Alvin Powers

Pancreatic islets are highly vascularized and this is important in insulin secretion

in response to nutrients like glucose. The purpose of this research was to investigate

the importance of vascular endothelial growth factor-A (VEGF-A) in adult islet function as

well as the function and morphology of intraislet vasculature. To accomplish this I used

a tamoxifen-inducible version of the Cre-loxP system (CreER). Two CreER transgenic

lines, (RIP-CreER or Pdx1PB-CreER) allowed for β-cell or islet-specific inactivation,

respectively, of VEGF-A following tamoxifen administration. RIP-CreER (Rat Insulin

Promoter) is expressed in β-cells of the islet while Pdx1PB-CreER is expressed in all islet

cell types. Cre-expressing mice were bred with Rosa26R (R26R) and Z/AP reporter

mice in order to test (A) the administration method of tamoxifen and (B) the

recombination efficiency. During these characterization studies we observed Cre

recombination in the absence of tamoxifen treatment in islets of RIP-CreER;R26R mice,

but not RIP-CreER;Z/AP mice. We found that Cre expression in RIP-CreER;R26R islets

was ~ 4X higher than Cre expression observed in Pdx1PB-CreER;R26R. These findings

indicate that Cre-mediated recombination of loxP sites depends both on the robustness

of the promoter driving CreER expression and the susceptibility of the targeted allele to

the Cre-mediated recombination.

Based on these findings, we crossed Pdx1PB-CreER transgenic mice with VEGFfl/fl

mice and measured the expression of VEGF-A in islets and the effects of VEGF-A

reduction on islet function and intraislet vasculature. We found that administration of

Tamoxifen effectively reduced VEGF-A levels in Pdx1PB-CreER; VEGFfl/fl mice. This

reduction in islet VEGF-A expression reduced islet vasculature, and transiently impaired

islet function.

These findings are particularly important for experiments utilizing inducible

systems. The results from our VEGF-A inactivation studies suggest that VEGF-A plays

a role in the maintenance of intra-islet vasculature in adults, and that reductions in islet

vascularization impact islet function.

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  jakantzfinal(2).pdf 144.94 Kb 00:00:40 00:00:20 00:00:18 00:00:09 < 00:00:01

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