Restoration of the Normal Splicing Pattern of the PLP1 Gene by Means of an Antisense Oligonucleotide Directed against an Exonic Mutation
Autor: | David N. Cooper, Stefano Regis, Fabio Corsolini, Serena Grossi, Mirella Filocamo, Barbara Tappino |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Pelizaeus-Merzbacher Disease
RNA Splicing Exonic splicing enhancer lcsh:Medicine Biology medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine medicine Missense mutation Humans RNA Messenger lcsh:Science Myelin Proteolipid Protein QH426 030304 developmental biology Genetics 0303 health sciences Mutation Multidisciplinary Point mutation lcsh:R Alternative splicing Pelizaeus–Merzbacher disease Exons Oligonucleotides Antisense medicine.disease R1 RNA splicing Mutagenesis Site-Directed lcsh:Q 030217 neurology & neurosurgery Research Article |
Zdroj: | PLoS ONE PLoS ONE; Vol 8 PLoS ONE, Vol 8, Iss 9, p e73633 (2013) |
ISSN: | 1932-6203 |
Popis: | An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells. |
Databáze: | OpenAIRE |
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