Mouse dystrophin exon 23 pre-messenger RNA (Mouse Dmd exon 23 pre-mRNA)

The exon 23 region of the mouse Dmd pre-messenger RNA (pre-mRNA) is a primary therapeutic target in the mdx mouse model of Duchenne muscular dystrophy (DMD). This specific region contains a C-to-T transition at base pair 3185, which creates a premature stop codon (UAA) that halts the translation of the dystrophin protein (Sicinski et al., 1989). Because the loss of dystrophin leads to progressive muscle wasting and fibrosis, this pre-mRNA site is targeted by antisense oligonucleotides (ASOs) designed to modulate splicing. These ASOs, such as phosphorodiamidate morpholino oligomers (PMOs) or 2'-O-methyl phosphorothioate (2'OMePS) molecules, bind to the exon 23 sequence or its splice junctions to induce 'exon skipping' (Mann et al., 2001; Alter et al., 2006). By excluding the mutated exon 23 from the mature mRNA, the reading frame between exons 22 and 24 is restored, enabling the production of a truncated but functional dystrophin protein (Lu et al., 2003). This target has served as the gold standard for proof-of-concept studies in the development of splice-switching therapies now used in human clinical practice.

Other names

mdx mutation siteDmd exon 23Mouse Dystrophin exon 23Dmd pre-mRNA exon 23Dystrophin exon 23

Antisense-mediated exon skipping (splice modulation)