Generation ofSki-knockdown mice by expressing a long double-strand RNA from an RNA polymerase II promoter

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Abstract
We have developed a new vector, named pDECAP, to express long double-strand RNA (ds-RNA) from an RNA polymerase II (Pol II) promoter. Because the transcripts from pDECAP lack both the 5′-cap structure and the 3′-poly(A) tail that facilitate ds-RNA export to the cytoplasm, long ds-RNA from pDECAP does not induce the interferon response. Transgenic mice embryos expressing long ds-RNA for the transcriptional corepressor Ski from this vector exhibited phenotypes that were remarkably similar to those ofSki-deficient embryos, including defects of neural tube closure and eye formation. Thus, this vector provides a new tool to efficiently generate tissue-specific knockdown mice for studying gene function in whole animal systems.