Hormonal and dietary regulation of a mammalian gene introduced into rat liver by direct injection.

Abstract

The difficulty of introducing foreign genes into a target tissue such as liver prompted us to explore the method of direct injection of DNA into this organ. In this article we examine whether direct hepatic injection of DNA enables the liver to express a transgene controlled by a mammalian promoter. The construct pS14CAT, composed of the rat S14 gene promoter coupled to CAT, was directly injected into rat liver. Hepatic expression of the pS14CAT transgene mimicked expression of the endogenous S14 gene, characterized by a low level of basal expression that increased markedly after exposure to thyroid hormone or a high sucrose diet. This effect was specific, since similar treatments had no effect on activity of a control transgene, pSV2CAT, which is under the direction of the viral SV40 promoter/enhancer. Dexamethasone treatment enhanced the activity of both pS14CAT or pSV2CAT transgenes, an effect likely mediated by both transcriptional and nontranscriptional pathways. In summary, our study demonstrates the feasibility of using direct DNA injection to study transcriptional regulation of hepatic gene promoters in vivo.