Tomita N, Morishita R, Higaki J, Tomita S, Aoki M, Kaneda Y, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Biochem Biophys Res Commun. 1996 Jul 5;224(1):43-9. doi: 10.1006/bbrc.1996.0982.
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.
尽管将肾素基因转染至成年肝脏会使血压（BP）在1周内升高，但要产生持续高血压的动物模型，必须考虑持续的转基因表达。我们推测，鉴于新生大鼠肝细胞具有高度增殖能力，将基因导入新生大鼠会导致长期的转基因表达。最初，将氯霉素乙酰转移酶（CAT）载体转染至1日龄大鼠的肝脏。免疫组织化学染色显示整个肝脏CAT呈阳性染色。因此，我们转染肾素载体以研究其生物学效应。在转染肾素载体的大鼠中，于第2周而非第4周和第8周观察到血浆血管紧张素II浓度显著升高。用肾素载体转染的肝脏中肾素mRNA的表达至少在6周内均可检测到，而血压未观察到显著变化。这些结果表明，将基因体内导入新生肝脏可导致转基因的持续表达，提示体内基因转移作为一种工具用于构建新型模型的潜力。
