title: Development of a novel transgenic rat overexpressing the P2Y(2) nucleotide receptor using a lentiviral vector.
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 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.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Mo. 65211, USA.
authors.forename: Cansu
authors.initials: C
authors.lastname: Agca
authors.forename: Cheikh
authors.initials: C
authors.lastname: Seye
authors.forename: Corinna M
authors.initials: CM
authors.lastname: Kashuba Benson
authors.forename: Shivaji
authors.initials: S
authors.lastname: Rikka
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
authors.forename: Gary A
authors.initials: GA
authors.lastname: Weisman
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Agca
mesh_terms: 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
chemical_list: C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2