We have used a lentiviral delivery system (LentiLox3.7) to generate transgenic mice harbouring RNA interference (RNAi) against the hepatocyte nuclear factor 4 gamma (HNF4gamma). HNF4gamma is a nuclear receptor with unknown function. Our analyses performed on founder (F(0)) and first generation (F(1)) mice revealed mosaicism in F(0) founders and a low efficiency of transgenesis (6%) in F(1) mice. These data, together with the observation of multiple silenced transgenes, do not favour the use of LentiLox3.7 lentivirus for transgenesis. Despite the low efficiency of transgenesis, we achieved a tissue-dependent knockdown of HNF4gamma expression in some mice.