Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA169527 | ENA |
REPOSITORIES: ENA
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Project description:Myotonic dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by an expanded CTG repeat that is transcribed into r(CUG)exp. The RNA repeat expansion sequesters regulatory proteins such as Muscleblind-like protein 1 (MBNL1), which causes pre-mRNA splicing defects. The disease-causing r(CUG)exp has been targeted by antisense oligonucleotides, CRISPR-based approaches, and RNA-targeting small molecules. Herein, we describe a designer small molecule, Cugamycin, that targets the structure of r(CUG)exp and cleaves it in cells and in vivo. Cugamycin selectively cleaves r(CUG)exp while leaving short repeats of r(CUG) untouched. In contrast, oligonucleotides that recognize r(CUG) sequence rather than structure cleave both long and short r(CUG)-containing transcripts. In the HSALR mouse model of DM1, Cugamycin selectively ablates r(CUG)exp in disease-affected muscle. Transcriptomic, histological, and phenotypic studies demonstrate that Cugamycin broadly and specifically relieves DM1-associated defects without detectable off-targets. Thus, small molecules that bind and cleave RNA may have utility as lead chemical probes and medicines.
2019-03-22 | GSE127809 | GEO
Project description:This study examined the effects of antisense oligonucleotides (ASOs) on the muscle transcriptome in a transgenic mouse model of myotonic dystrophy. Two ASOs were tested in HSALR transgenic mice. Both of the ASOs targeted mRNA from a human skeletal actin (hACTA1) transgene. This transgene contains an expanded CTG repeat in the 3’ untranslated region (UTR) (Mankodi et al “Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat” Science 2000; 289:1769-72). ASO 445235 targeted the hACTA1 transcript in the 3’ UTR, downstream from the expanded repeat. ASO 190401 targeted the hACTA1 transcript in the coding region. The HSALR mice received 4 weeks of biweekly subcutaneous injections of vehicle (saline), ASO 190401, or ASO 445236 (n = 4 per group), at a dose of 25 mg/kg per injection. Wild-type mice of the same strain background received saline injections (n = 4). One week after the final injection, quadriceps muscle was harvested for RNA analysis.
2012-06-28 | GSE38962 | GEO
Project description:This study examined the effects of antisense oligonucleotides (ASOs) on the muscle transcriptome in a transgenic mouse model of myotonic dystrophy. Two ASOs were tested in HSALR transgenic mice. Both of the ASOs targeted mRNA from a human skeletal actin (hACTA1) transgene. This transgene contains an expanded CTG repeat in the 3M-bM-^@M-^Y untranslated region (UTR) (Mankodi et al M-bM-^@M-^\Myotonic dystrophy in transgenic mice expressing an expanded CUG repeatM-bM-^@M-^] Science 2000; 289:1769-72). ASO 445235 targeted the hACTA1 transcript in the 3M-bM-^@M-^Y UTR, downstream from the expanded repeat. ASO 190401 targeted the hACTA1 transcript in the coding region. The HSALR mice received 4 weeks of biweekly subcutaneous injections of vehicle (saline), ASO 190401, or ASO 445236 (n = 4 per group), at a dose of 25 mg/kg per injection. Wild-type mice of the same strain background received saline injections (n = 4). One week after the final injection, quadriceps muscle was harvested for RNA analysis. Four conditions, four arrays per condition, to compare WT and HSALR trangenic mice without treatment (saline) and to examine the effect of two oligos (vs. saline) in the HSALR transgenic mice.
2012-06-27 | E-GEOD-38962 | biostudies-arrayexpress
Project description:In this Study, we used RNA-targeting Cas9 (RCas9) to reverse characteristic Myotonic Dystrophy (DM1) cellular phenotypes such as elimination of RNA foci, MBNL relocalization, and reversal of transcriptome-wide splicing in a mouse model of myotonic Dystrophy (DM1). Furthermore we show that gene expression is not altered with RCas9 treatment in WT mice with or without treatment with immunosuppression
2020-07-01 | GSE152033 | GEO
Project description:Misregulated alternative splicing appears to be a major factor in the pathogenesis of myotonic dystrophy. The present study was done to further explore alternative splicing in this condition by doing exon-level analysis of mRNA from skeletal muscle of 8 subjects with type 1 myotonic dystrophy, 7 subjects with type 2 myotonic dystrophy, 8 disease controls (subjects with facioscapulohumeral muscular dystrophy), and 8 healthy controls . The ratios of signals from the various exons of a gene provided an index of altered exon inclusion/exclusion that was independent of the overall expression of that gene. There were numerous transcripts for which there was evidence of abnormal alternative splicing in subjects with myotonic dystrophy. For many of these transcripts, the abnormal splicing was confirmed by an independent RT-PCR approach. 31 subjects, one sample per subject, four groups: healthy subjects (n = 8), facioscapulohumeral dystrophy (n = 8), type 1 myotonic dystrophy (n = 8), type 2 myotonic dystrophy (n = 7)
2013-06-15 | E-GEOD-47968 | biostudies-arrayexpress
Project description:Compound loss of muscleblind-like function in myotonic dystrophy
| PRJNA207816 | ENA
Project description:Comparison of myotonic dystrophy cataract samples with control non-myotonic dystrophy cataract samples
2011-10-31 | E-MEXP-3365 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:In this Study, we used RNA-targeting Cas9 (RCas9) to reverse characteristic Myotonic Dystrophy (DM1) cellular phenotypes such as elimination of RNA foci, MBNL relocalization, and reversal of transcriptome-wide splicing.
2017-08-10 | GSE100943 | GEO