Sustained transgene expression by transfection of renin gene into liver of neonates.

Although transfection of renin gene into adult liver resulted in increased blood pressure (BP) for 1 week, sustained transgene expression must be considered to produce a continuous hypertensive animal. We hypothesized that gene transfer into neonatal rats would result in long-term transgene expression, given with highly replicating hepatocytes in neonates. Initially, chloramphenicol acetyltransferase (CAT) vector was transfected into the liver of 1-day-old rats. Immunohistochemical staining showed positive staining of CAT throughout the liver. Therefore, we transfected renin vector to study biological effects. At 2, but not 4 and 8, weeks, a significant increase in plasma angiotensin II concentration was observed in rats transfected with renin vector. Expression of renin mRNA in the liver transfected with renin vector could be detected at least up to 6 weeks, while no significant changes in BP were observed. These results demonstrated that in vivo gene transfer into the neonatal liver resulted in sustained transgene expression, suggesting the potential use of in vivo gene transfer as a tool to produce a novel model.