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Gene silencing with double-stranded RNA (RNAi) has proved useful for gene function studies, and should be especially well suited to studying diseases resulting in embryonal lethality where transgenic animal models are difficult to generate. We are applying this approach to the autosomal recessive disease spinal muscular atrophy (SMA). SMA is caused by mutations in the survival of motor neuron gene (SMN). The SMN protein is ubiquitously expressed and plays a role in RNA processing and its reduction in SMA ultimately leads to motor neuron degeneration in the spinal cord. The reasons for this motor neuron selectivity, however, are still unclear. SMN is essential for the viability of most eukaryotic organisms and this has made the generation of animal models of SMA extremely difficult. Here we describe a different approach to study SMN function using RNAi to silence SMN expression in cells. We designed double-stranded small interfering RNA (siRNA) targeted against murine Smn and transfected the murine embryonal terato-carcinoma cell line P19. The siRNAs reduced both Smn RNA and protein levels in the P19 cells compared to controls. These results illustrate that double-stranded RNA can be an effective gene silencing approach even in a protein that is essential for survival and highly expressed, and it could therefore be a valuable tool to study SMN function.

Original publication




Journal article


Brain Res Mol Brain Res

Publication Date





145 - 150


Animals, Blotting, Western, Carcinoma, Cell Line, Tumor, Cyclic AMP Response Element-Binding Protein, Disease Models, Animal, Down-Regulation, Embryo, Mammalian, Gene Silencing, Mice, Motor Neurons, Muscular Atrophy, Spinal, Nerve Tissue Proteins, Propidium, RNA, Double-Stranded, RNA, Messenger, RNA, Small Interfering, RNA-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, SMN Complex Proteins, Time Factors, Transfection