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Author Notes:

Dr. Yuksel Agca, Department of Veterinary Pathobiology University of Missouri, College of Veterinary Medicine 1600 East Rollins Rd., Columbia, MO 65211 (USA) Tel. +1 573 884 0311, Fax +1 573 884 7827, agcay@missouri.edu.

The authors also would like to acknowledge Howard Wilson for his assistance with the images.

Subjects:

Research Funding:

This study was supported by NIH grants AG18357, DE07389, DE017591; and MU start-up funds.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physiology
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • P2Y(2) receptor
  • Nucleotide
  • Sjogren's syndrome, transgenic rat
  • PRIMARY SJOGRENS-SYNDROME
  • SUBMANDIBULAR-GLAND
  • ENDOTHELIAL-CELLS
  • CYSTIC-FIBROSIS
  • P2 RECEPTORS
  • STEM-CELLS
  • EXPRESSION
  • EMBRYOS
  • GENE
  • ATP

Development of a Novel Transgenic Rat Overexpressing the P2Y(2) Nucleotide Receptor Using a Lentiviral Vector

Tools:

Journal Title:

Journal of Vascular Research

Volume:

Volume 46, Number 5

Publisher:

, Pages 447-458

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The G protein-coupled P2Y 2 nucleotide receptor (P2Y 2 R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjögren's syndrome. The role of P2Y 2 R upregulation in vivo is poorly understood, in part due to the lack of a P2Y 2 R overexpressing animal model. The P2Y 2 R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y 2 R showed a significant increase in P2Y 2 R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y 2 R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y 2 R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjögren's syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y 2 R overexpression may prove useful for linking P2Y 2 R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren's syndrome.

Copyright information:

Copyright © 2009 S. Karger AG.

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