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Comment
. 2014 Nov;22(11):1884-6.
doi: 10.1038/mt.2014.189.

Could exon skipping help dystrophic boys to run, hop, and jump?

Terence Partridge  1
Affiliations
Comment

Could exon skipping help dystrophic boys to run, hop, and jump?

Terence Partridge. Mol Ther. 2014 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Rationale of exon skipping in the GRMD dog. Codon triplet boundaries often do not coincide with exon boundaries as in exon 6, 7, and 8 of the dystrophin gene (a); in the normal gene, the functional triplet codon is maintained by splicing the two nucleotides 3′ of exon 6 to the single 5′ nucleotide of exon 7. Similarly, the trailing single nucleotide on exon 7 is complemented by the two leading nucleotides of exon 8. In the GRMD (golden retriever muscular dystrophy) dog, a point mutation in the 5′ splice site of exon 7 prevents it from being spliced into the messenger RNA transcript of the dystrophin gene (b), resulting in a failure to maintain the reading frame of codons beyond this point (c). This eventually leads to a nonsense codon with consequent termination of translation and nonsense-mediated decay of the aberrant transcript. To restore an open reading frame, it is necessary to eliminate at least two further codons from the transcript (d). Because exon and codon boundaries coincide in both exons 5 and 9 (e), a translatable transcript is produced when the two are spliced together.
See this image and copyright information in PMC

Comment on

  • Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients.
    Le Guiner C, Montus M, Servais L, Cherel Y, Francois V, Thibaud JL, Wary C, Matot B, Larcher T, Guigand L, Dutilleul M, Domenger C, Allais M, Beuvin M, Moraux A, Le Duff J, Devaux M, Jaulin N, Guilbaud M, Latournerie V, Veron P, Boutin S, Leborgne C, Desgue D, Deschamps JY, Moullec S, Fromes Y, Vulin A, Smith RH, Laroudie N, Barnay-Toutain F, Rivière C, Bucher S, Le TH, Delaunay N, Gasmi M, Kotin RM, Bonne G, Adjali O, Masurier C, Hogrel JY, Carlier P, Moullier P, Voit T. Le Guiner C, et al. Mol Ther. 2014 Nov;22(11):1923-35. doi: 10.1038/mt.2014.151. Epub 2014 Aug 4. Mol Ther. 2014. PMID: 25200009 Free PMC article.

References

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