| Summary: | 碩士 === 國立中正大學 === 分子生物研究所 === 101 === Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by expanded CUG repeat RNA. Our laboratory has established a C. elegans model of DM1 and further demonstrated that the DM1 phenotypes could be alleviated by decreasing the expression of CUG repeat RNA. In this study, we aimed to identify the DM1 genetic modifiers required for efficient expression of expanded CUG repeats using genome-wide RNAi approach. By microscopy observation, I picked up 8 candidates RNAi clones which may contain gene(s) required for efficient expression of GFP reporter gene containing (CTG)83 repeats. Two of these candidates, Y73F8A.f and Y73F8A.g, can extend the life span of CUG125 worms. Subsequent database analysis revealed that clone Y73F8A.f may target to ccg-1 gene. Indeed, ccg-1 RNAi treatment reduced the expression of CUG125 RNA and its effect on the life span of worms. By contrast, ccg-1 RNAi treatment did not affect the gfp expression and life span of CUG0 worms. These results suggest that ccg-1 is specifically required for efficient expression of expanded CUG repeats and can function as a genetic modifier of CUG RNA toxicity.
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