Development of a novel transgenic rat overexpressing the P2Y(2) nucleotide receptor using a lentiviral vector.
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 Sjogren'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 Sjogren'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 Sjogren's syndrome.
Agca
Cansu
C
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Mo. 65211, USA.
Seye
Cheikh
C
Kashuba Benson
Corinna M
CM
Rikka
Shivaji
S
Chan
Anthony W S
AW
Weisman
Gary A
GA
Agca
Yuksel
Y
D000818:Animals; D021461:Animals, Outbred Strains; D001011:Aorta / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006720:Homozygote; D016086:Lentivirus / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058473:Receptors, Purinergic P2Y2; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019076:Transgenes / Q000235:genetics
C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2