A transgenic approach for RNA interference-based genetic screening in mice.

Genetic screening is the most powerful method through which to uncover gene function. It has been applied very successfully in lower organisms but seldom attempted in mammalian species because of their long generation time. In this study, we exploit RNA interference (RNAi) for its potential use in genetic screening in mice. We show that RNAi-induced gene knockdown can be generated through introducing small hairpin RNA-expressing constructs into the mouse as transgenes via conventional pronuclear injection. The knockdown effect can be transmitted for many generations in these transgenic animals. In a small-scale screening for developmental defects in the kidney, we uncovered a potential role of Id4 in the formation of the renal medulla. Our results demonstrate the feasibility of using RNAi for genetic screening in mice.