dc.contributor.author
Malcher, Jakub
dc.contributor.author
Heidt, Leonie
dc.contributor.author
Goyenvalle, Aurélie
dc.contributor.author
Escobar, Helena
dc.contributor.author
Marg, Andreas
dc.contributor.author
Beley, Cyriaque
dc.contributor.author
Benchaouir, Rachid
dc.contributor.author
Bader, Michael
dc.contributor.author
Spuler, Simone
dc.contributor.author
García, Luis
dc.contributor.author
Schöwel, Verena
dc.date.accessioned
2019-04-01T08:51:49Z
dc.date.available
2019-04-01T08:51:49Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24238
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2010
dc.description.abstract
Limb girdle muscular dystrophy 2B (LGMD2B) is without treatment and caused by mutations in the dysferlin gene (DYSF). One-third is missense mutations leading to dysferlin aggregation and amyloid formation, in addition to defects in sarcolemmal repair and progressive muscle wasting. Dysferlin-null mouse models do not allow study of the consequences of missense mutations. We generated a new mouse model (MMex38) carrying a missense mutation in exon 38 in analogy to a clinically relevant human DYSF variant (DYSF p.Leu1341Pro). The targeted mutation induces all characteristics of missense mutant dysferlinopathy, including a progressive dystrophic pattern, amyloid formation, and defects in membrane repair. We chose U7 small nuclear RNA (snRNA)-based splice switching to demonstrate a possible exon-skipping strategy in this new animal model. We show that Dysf exons 37 and 38 can successfully be skipped in vivo. Overall, the MMex38 mouse model provides an ideal tool for preclinical development of treatment strategies for dysferlinopathy.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Exon skipping in a dysf-missense mutant mouse model
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1016/j.omtn.2018.08.013
dcterms.bibliographicCitation.journaltitle
Molecular Therapy: Nucleic Acids
dcterms.bibliographicCitation.originalpublishername
Elsevier
dcterms.bibliographicCitation.pagestart
198
dcterms.bibliographicCitation.pageend
207
dcterms.bibliographicCitation.volume
13
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30292141
dcterms.isPartOf.issn
2162-2531