Dystrophin pre-messenger RNA exon 23 (Dmd exon 23) (Dmd exon 23)

The mdx mouse dystrophin pre-messenger RNA exon 23 is a critical therapeutic target in preclinical research for Duchenne muscular dystrophy (DMD). In the mdx mouse model, a spontaneous nonsense mutation (C-to-T transition) at position 3185 in exon 23 of the Dmd gene introduces a premature stop codon (UAA), which halts the translation of the full-length dystrophin protein (Sicinski et al., Science, 1989). Dystrophin is a vital cytoskeletal protein that maintains the structural integrity of the sarcolemma; its absence leads to progressive muscle wasting, fibrosis, and loss of function. Therapeutic interventions, primarily antisense oligonucleotides (ASOs), are designed to bind to specific sequences within or adjacent to exon 23 to induce "exon skipping" (Mann et al., PNAS, 2001). By masking the splice donor or acceptor sites, the splicing machinery bypasses the mutated exon, restoring the mRNA reading frame. This results in the production of a truncated but partially functional dystrophin protein, effectively converting a severe DMD-like phenotype into a milder Becker muscular dystrophy-like phenotype (Lu et al., Nature Medicine, 2003). This target is also a focus for gene editing strategies using CRISPR/Cas9 to permanently excise the mutated exon and restore protein expression (Long et al., Science, 2014).

Other names

mdx exon 23Dmd exon 23 nonsense mutation siteMouse dystrophin exon 23Dystrophin pre-mRNA exon 23

Antisense-mediated exon skipping to restore the translational reading frame