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- Title
Development of a Novel Transgenic Rat Overexpressing the P2Y<sub>2</sub> Nucleotide Receptor Using a Lentiviral Vector.
- Authors
Agca, Cansu; Seye, Cheikh; Benson, Corinna M. Kashuba; Rikka, Shivaji; Chan, Anthony W. S.; Weisman, Gary A.; Agca, Yuksel
- Abstract
The G protein-coupled P2Y2 nucleotide receptor (P2Y2R) 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 P2Y2R upregulation in vivo is poorly understood, in part due to the lack of a P2Y2R overexpressing animal model. The P2Y2R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y2R showed a significant increase in P2Y2R 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 P2Y2R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y2R 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 P2Y2R overexpression may prove useful for linking P2Y2R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren’s syndrome. Copyright © 2009 S. Karger AG, Basel
- Subjects
NEURODEGENERATION; NUCLEOTIDES; PROMOTERS (Genetics); NUCLEIC acids; MEMBRANE proteins
- Publication
Journal of Vascular Research, 2009, Vol 46, Issue 5, p447
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000194274