rdf:type |
|
lifeskim:mentions |
umls-concept:C0015295,
umls-concept:C0026847,
umls-concept:C0035647,
umls-concept:C0035696,
umls-concept:C0087111,
umls-concept:C0205217,
umls-concept:C0335038,
umls-concept:C1367790,
umls-concept:C1420258,
umls-concept:C1512693,
umls-concept:C1515655
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pubmed:issue |
20
|
pubmed:dateCreated |
2001-11-12
|
pubmed:abstractText |
Spinal muscular atrophy (SMA) is a degenerative motor neuron disorder resulting from homozygous loss of the SMN1 gene. SMN2, a nearly identical copy gene, is preserved in SMA patients. A single nucleotide difference between SMN1 and SMN2 causes exon 7 skipping in the majority of SMN2 mRNA. Gene therapy through modulation of SMN2 gene transcription in SMA patients may be possible. We constructed a series of SMN mini-genes comprised of SMN exon 6 to exon 8 sequences fused to green fluorescence protein (GFP) or luciferase reporters, to monitor SMN exon 7 splicing. These reporters recapitulated the splicing patterns of the endogenous SMN gene in stable cell lines. The SMN1-luciferase reporter was approximately 3.5-fold more active than SMN2-luciferase and SMN1-GFP intensities were visually distinguishable from SMN2-GFP. We have screened chemical inducers and inhibitors of kinase pathways using stable SMN-reporter lines and found that the phosphatase inhibitor sodium vanadate specifically stimulated exon 7 inclusion within SMN2 mRNAs. This is the first compound identified that can stimulate exon 7 inclusion into transcripts derived from the endogenous SMN2 gene. These results demonstrate that this system can be utilized to identify small molecules that regulate the splicing of SMN exon 7.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMN Complex Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMN2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Survival of Motor Neuron 1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Survival of Motor Neuron 2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Vanadates
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
|
pubmed:issn |
0969-7128
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
8
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
1532-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11704813-Artificial Gene Fusion,
pubmed-meshheading:11704813-Cell Line,
pubmed-meshheading:11704813-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:11704813-Enzyme Inhibitors,
pubmed-meshheading:11704813-Exons,
pubmed-meshheading:11704813-Gene Expression,
pubmed-meshheading:11704813-Gene Therapy,
pubmed-meshheading:11704813-Green Fluorescent Proteins,
pubmed-meshheading:11704813-Humans,
pubmed-meshheading:11704813-Luciferases,
pubmed-meshheading:11704813-Luminescent Proteins,
pubmed-meshheading:11704813-Motor Neurons,
pubmed-meshheading:11704813-Muscular Atrophy, Spinal,
pubmed-meshheading:11704813-Nerve Tissue Proteins,
pubmed-meshheading:11704813-Phosphoric Monoester Hydrolases,
pubmed-meshheading:11704813-Phosphorylation,
pubmed-meshheading:11704813-RNA Splicing,
pubmed-meshheading:11704813-RNA-Binding Proteins,
pubmed-meshheading:11704813-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11704813-SMN Complex Proteins,
pubmed-meshheading:11704813-Survival of Motor Neuron 1 Protein,
pubmed-meshheading:11704813-Survival of Motor Neuron 2 Protein,
pubmed-meshheading:11704813-Transfection,
pubmed-meshheading:11704813-Vanadates
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pubmed:year |
2001
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pubmed:articleTitle |
An in vivo reporter system for measuring increased inclusion of exon 7 in SMN2 mRNA: potential therapy of SMA.
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pubmed:affiliation |
Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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