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By introducing double-stranded RNAs (dsRNAs), it was shown that mRNAs that share sequences are destroyed, and that the translation step is severely downregulated (RNAi). This technique was demonstrated to be a very powerful tool for reverse genetics in
Caenorhabditis elegans
. However, studies have shown that RNAi can be achieved in living mice. In this chapter, we used “green mice” and “green rats” as model animals to demonstrate silencing of green fluorescent protein (GFP) expression by RNAi. In order to silence the gene, we produced transgenic mouse lines that produce dsRNA that is driven by the H1 promoter. It was demonstrated that the transgenically expressed, double stranded RNA could silence the GFP throughout the body of the mouse or rat and throughout the lifetime.