| Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. | |
| | |
MedLine Citation:
|
PMID: 22427994 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by a CTG trinucleotide repeat expansion (CTG(exp)) in the DMPK gene. In skeletal muscle, nuclear sequestration of the alternative splicing factor muscleblind-like 1 (MBNL1) explains the majority of the alternative splicing defects observed in the HSA(LR) transgenic mouse model which expresses a pathogenic range CTG(exp). In the present study, we addressed the possibility that MBNL1 sequestration by CUG(exp) RNA also contributes to splicing defects in the mammalian brain. We examined RNA from the brains of homozygous Mbnl1(ΔE3/ΔE3) knockout mice using splicing-sensitive microarrays. We used RT-PCR to validate a subset of alternative cassette exons identified by microarray analysis with brain tissues from Mbnl1(ΔE3/ΔE3) knockout mice and post-mortem DM1 patients. Surprisingly, splicing-sensitive microarray analysis of Mbnl1(ΔE3/ΔE3) brains yielded only 14 candidates for mis-spliced exons. While we confirmed that several of these splicing events are perturbed in both Mbnl1 knockout and DM1 brains, the extent of splicing mis-regulation in the mouse model was significantly less than observed in DM1. Additionally, several alternative exons, including Grin1 exon 4, App exon 7 and Mapt exons 3 and 9, which have previously been reported to be aberrantly spliced in human DM1 brain, were spliced normally in the Mbnl1 knockout brain. The sequestration of MBNL1 by CUG(exp) RNA results in some of the aberrant splicing events in the DM1 brain. However, we conclude that other factors, possibly other MBNL proteins, likely contribute to splicing mis-regulation in the DM1 brain. |
| | |
Authors:
|
Koichi Suenaga; Kuang-Yung Lee; Masayuki Nakamori; Yoshiki Tatsumi; Masanori P Takahashi; Harutoshi Fujimura; Kenji Jinnai; Hiroo Yoshikawa; Hongqing Du; Manuel Ares; Maurice S Swanson; Takashi Kimura |
Related Documents
:
|
11504884 - Conditional cell ablation by stringent tetracycline-dependent regulation of barnase in ... 1372564 - Expression analysis of ruminant alpha-lactalbumin in transgenic mice: developmental reg... 8074994 - Germ-line expression of a functional line from drosophila melanogaster: fine characteri... 17637794 - Regulated expression of the interferon-beta gene in mice. 8380064 - Antisense suppression of transferrin receptor gene expression in a human hepatoma cell ... 8662914 - Sv40 large t antigen transactivates the human cdc2 promoter by inducing a ccaat box bin... |
Publication Detail:
|
Type: Journal Article Date: 2012-03-13 |
Journal Detail:
|
Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012 |
Date Detail:
|
Created Date: 2012-03-19 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
|
Languages: eng Pagination: e33218 Citation Subset: IM |
Affiliation:
|
Division of Neurology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A putative cell surface receptor for white spot syndrome virus is a member of a transporter superfam...
Next Document: Grapevine Aquaporins: Gating of a Tonoplast Intrinsic Protein (TIP2;1) by Cytosolic pH.