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Evidence for toxic CAG trinucleotide repeats contributing to Huntington’ease though RNA interference I

ABSTRACT: Evidence for toxic CAG trinucleotide repeats contributing to Huntington’ease though RNA interference I

PROVIDER: PRJNA832696 | ENA |

REPOSITORIES: ENA

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Evidence for toxic CAG trinucleotide repeats contributing to Huntington’ease though RNA interference II

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Transcription profiling of mouse cerebellum cells containing expanded or normal CAG trinucleotide repeats in the coding region for TATA-binding protein (TBP)

Project description:Transcription profiles were obtained for 2-month old mice containing an expanded or normal CAG trinucleotide repeat in the coding region for TATA-binding protein (TBP). Three different genotypes were used : TBP-13Q (normal), TBP-71Q (71 repeats), and TBP-105Q (105 repeats). Two lines of TBP-71Q (lines 16 and 27) were used in these experiments. <br><br> The 71Q and 105Q mice express a mutant version of the protein (TBP) and faithfully model the disease SCA17 (spinocerebellar ataxia-17, huntington disease-like 4, HDL4). <br><br> The constructs containing mixed CAG/CAA trinucleotide repeats (and encoding polyglutamine tracts) of variable length were made using a previously described method (Michalik A et al., Biotechniques, 2001). Briefly, synthetic CAG/CAA oligonucleotides were subcloned into a cDNA construct of the normal mouse (13 CAG/CAA) TBP gene. Because of the mixed nature of the repeat, its length is stable in mitotic and meiotic transmission.

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Reversion of FMR1 methylation and silencing by editing the triplet repeats in Fragile-X iPSC-derived neurons

Project description:Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Here we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders.

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Study of variants associated with Fuchs corneal endothelial dystrophy cases without expansion of CTG18.1 repeats

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Deregulation of alternative splicing by toxic CUG repeats in astrocytes from a mouse model of myotonic dystrophy

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Expression data from SCA3 and genetically corrected iPSCs

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