Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.

Détails

ID Serval
serval:BIB_BD74D6C000A6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.
Périodique
Human molecular genetics
Auteur(s)
Meyer Kathrin, Marquis Julien, Trub Judith, Nlend Nlend Rachel, Verp Sonia, Ruepp Marc-David, Imboden Hans, Barde Isabelle, Trono Didier, Schumperli Daniel
Statut éditorial
Publié
Date de publication
02/2009
Volume
18
Numéro
3
Pages
546-555
Langue
anglais
Résumé
In spinal muscular atrophy (SMA), the leading genetic cause of early childhood death, the survival motor neuron 1 gene (SMN1) is deleted or inactivated. The nearly identical SMN2 gene has a silent mutation that impairs the utilization of exon 7 and the production of functional protein. It has been hypothesized that therapies boosting SMN2 exon 7 inclusion might prevent or cure SMA. Exon 7 inclusion can be stimulated in cell culture by oligonucleotides or intracellularly expressed RNAs, but evidence for an in vivo improvement of SMA symptoms is lacking. Here, we unambiguously confirm the above hypothesis by showing that a bifunctional U7 snRNA that stimulates exon 7 inclusion, when introduced by germline transgenesis, can efficiently complement the most severe mouse SMA model. These results are significant for the development of a somatic SMA therapy, but may also provide new means to study pathophysiological aspects of this devastating disease.
Mots-clé
Animals, Base Sequence, Humans, Mice, Mice, Transgenic, *Genetic Therapy, Exons, Molecular Sequence Data, Muscular Atrophy, Spinal/*genetics/metabolism/*therapy, RNA Splicing, RNA, Small Nuclear/genetics/*therapeutic use, Survival of Motor Neuron 2 Protein/genetics/metabolism
Pubmed
Création de la notice
19/02/2020 13:23
Dernière modification de la notice
19/06/2020 6:26
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