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Series GSE14691 Query DataSets for GSE14691
Status Public on Feb 05, 2009
Title Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy
Organism Mus musculus
Experiment type Expression profiling by array
Summary Myotonic dystrophy type 1 (DM1) is an RNA dominant disease in which mutant transcripts containing an expanded CUG repeat (CUGexp) cause muscle dysfunction by interfering with biogenesis of other mRNAs. The toxic effects of mutant RNA are mediated partly through sequestration of splicing regulator Muscleblind-like 1 (Mbnl1), a protein that binds to CUGexp RNA. A gene that is prominently affected encodes chloride channel 1 (Clcn1), resulting in hyperexcitability of muscle (myotonia). To identify DM1-affected genes and study mechanisms for dysregulation, we performed global mRNA profiling in transgenic mice that express CUGexp RNA, as compared to Mbnl1 knockout and Clcn1 null mice. We found that the majority of changes induced by CUGexp RNA in skeletal muscle can be explained by reduced activity of Mbnl1, including many changes that are secondary to myotonia. The pathway most affected comprises genes involved in calcium signaling and homeostasis. Some effects of CUGexp RNA on gene expression are caused by abnormal alternative splicing or downregulation of Mbnl1-interacting mRNAs. However, several of the most highly dysregulated genes showed altered transcription, as indicated by parallel changes of the corresponding premRNAs. These results support the idea that trans-dominant effects of CUGexp RNA on gene expression in this transgenic model may occur at the level of transcription, RNA processing, and mRNA decay, and are mediated mainly but not entirely through sequestration of Mbnl1.

Keywords: comparison of normal and transgenic mice
Overall design All experiments involved generating expression profiles of quadriceps muscles taken from mice. Experiments 1 and 2: samples were hybridized to Moe430A and Moe430B arrays. Experiment 3: samples were hybridized to Mouse Genome 430 2.0 array. Experiment 1 compared expression profiles of wild-type mice (FVB strain) with two lines, designated 20b and 41, of CUGexp transgenic mice with FVB background. Experiment 2 compared expression profiles of Clcn1-null (myotonic) mice with the wild-type background strain (BALB). Experiment 3 compared expression profiles of Mbnl1-null mice with the wild-type background strain (FVB).
Contributor(s) Welle S, Thornton CA
Citation(s) 19223393
Submission date Feb 03, 2009
Last update date Feb 11, 2019
Contact name Stephen Welle
Organization name University of Rochester
Street address 601 Elmwood Avenue
City Rochester
State/province NY
ZIP/Postal code 14642
Country USA
Platforms (3)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
GPL340 [MOE430B] Affymetrix Mouse Expression 430B Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (58)
GSM366793 Line 41 1_Experiment 1, 430A
GSM366794 Line 41 2_Experiment 1, 430A
GSM366795 Line 41 3_Experiment 1, 430A
BioProject PRJNA111683

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE14691_RAW.tar 231.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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