We recently developed a novel kidney-targeted gene transfer technique in rats, using the retrograde renal vein injection of naked plasmid DNA. Many animal disease models are created in mice by transgenic or knockout technologies. However, it is much harder to perform renal vein injection in mice than in rats because they have a thin and short vein. Here we transferred the mouse interleukin (IL)-10 gene into mice by retrograde renal vein injection, using an IL-10 and immunoglobulin fusion protein (IL-10/Fc) (96-kDa) expression plasmid, pCAGGS-IL10/Fc. We observed a dose-response relationship between serum IL-10 levels and the amount of injected DNA. The serum IL-10 levels peaked at day 1 and then were sustained for at least 2 weeks. These results demonstrate that the kidney-targeted naked plasmid DNA transfer of mice by retrograde renal vein injection can be achieved, and the kidney serves as a depot organ for the production of large proteins. (C) 2003 Elsevier Inc. All rights reserved.