Germ line transmission and expression of an RNAi cassette in mice generated by a lentiviral vector system

We have used a lentiviral delivery system (LentiLox3.7) to generate transgenic mice harbouring RNA interference (RNAi) against the hepatocyte nuclear factor 4 gamma (HNF4γ). HNF4γ is a nuclear receptor with unknown function. Our analyses performed on founder (F₀) and first generation (F₁) mice revealed mosaicism in F₀ founders and a low efficiency of transgenesis (6%) in F₁ 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 HNF4γ expression in some mice. Milen Kirilov and Minqiang Chai contributed equally to this work.